Review
. 2022 Jan; 21(1):28.
doi: 10.1186/s12943-021-01489-2.

Combination strategies with PD-1/PD-L1 blockade: current advances and future directions

Ming Yi 1 Xiaoli Zheng 2 Mengke Niu 1 Shuangli Zhu 1 Hong Ge 3 Kongming Wu 4 
Affiliations
  • PMID: 35062949
  •     326 References
  •     4 citations

Abstract

Antibodies targeting programmed cell death protein-1 (PD-1) or its ligand PD-L1 rescue T cells from exhausted status and revive immune response against cancer cells. Based on the immense success in clinical trials, ten α-PD-1 (nivolumab, pembrolizumab, cemiplimab, sintilimab, camrelizumab, toripalimab, tislelizumab, zimberelimab, prolgolimab, and dostarlimab) and three α-PD-L1 antibodies (atezolizumab, durvalumab, and avelumab) have been approved for various types of cancers. Nevertheless, the low response rate of α-PD-1/PD-L1 therapy remains to be resolved. For most cancer patients, PD-1/PD-L1 pathway is not the sole speed-limiting factor of antitumor immunity, and it is insufficient to motivate effective antitumor immune response by blocking PD-1/PD-L1 axis. It has been validated that some combination therapies, including α-PD-1/PD-L1 plus chemotherapy, radiotherapy, angiogenesis inhibitors, targeted therapy, other immune checkpoint inhibitors, agonists of the co-stimulatory molecule, stimulator of interferon genes agonists, fecal microbiota transplantation, epigenetic modulators, or metabolic modulators, have superior antitumor efficacies and higher response rates. Moreover, bifunctional or bispecific antibodies containing α-PD-1/PD-L1 moiety also elicited more potent antitumor activity. These combination strategies simultaneously boost multiple processes in cancer-immunity cycle, remove immunosuppressive brakes, and orchestrate an immunosupportive tumor microenvironment. In this review, we summarized the synergistic antitumor efficacies and mechanisms of α-PD-1/PD-L1 in combination with other therapies. Moreover, we focused on the advances of α-PD-1/PD-L1-based immunomodulatory strategies in clinical studies. Given the heterogeneity across patients and cancer types, individualized combination selection could improve the effects of α-PD-1/PD-L1-based immunomodulatory strategies and relieve treatment resistance.

Keywords: Angiogenesis inhibitor; Bispecific antibody; Combination therapy; Gut microbiota; PD-1; PD-L1; Radiotherapy; STING.

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Exp Hematol Oncol, 2021 Oct 29; 10(1). PMID: 34706782    Free PMC article.
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Camrelizumab Plus Apatinib in Extensive-Stage SCLC (PASSION): A Multicenter, Two-Stage, Phase 2 Trial.
Yun Fan, Jun Zhao, +18 authors, Jie Wang.
J Thorac Oncol, 2020 Nov 10; 16(2). PMID: 33166719
cGAS produces a 2'-5'-linked cyclic dinucleotide second messenger that activates STING.
Andrea Ablasser, Marion Goldeck, +6 authors, Veit Hornung.
Nature, 2013 Jun 01; 498(7454). PMID: 23722158    Free PMC article.
Highly Cited.
A Phase I Trial of Regional Mesothelin-Targeted CAR T-cell Therapy in Patients with Malignant Pleural Disease, in Combination with the Anti-PD-1 Agent Pembrolizumab.
Prasad S Adusumilli, Marjorie G Zauderer, +27 authors, Michel Sadelain.
Cancer Discov, 2021 Jul 17; 11(11). PMID: 34266984    Free PMC article.
Neoadjuvant durvalumab with or without stereotactic body radiotherapy in patients with early-stage non-small-cell lung cancer: a single-centre, randomised phase 2 trial.
Nasser K Altorki, Timothy E McGraw, +16 authors, Silvia C Formenti.
Lancet Oncol, 2021 May 21; 22(6). PMID: 34015311
Doxorubicin eliminates myeloid-derived suppressor cells and enhances the efficacy of adoptive T-cell transfer in breast cancer.
Darya Alizadeh, Malika Trad, +5 authors, Nicolas Larmonier.
Cancer Res, 2013 Nov 08; 74(1). PMID: 24197130    Free PMC article.
Highly Cited.
Randomized Phase II Trial of Nivolumab With Stereotactic Body Radiotherapy Versus Nivolumab Alone in Metastatic Head and Neck Squamous Cell Carcinoma.
Sean McBride, Eric Sherman, +16 authors, Nancy Lee.
J Clin Oncol, 2020 Aug 22; 39(1). PMID: 32822275    Free PMC article.
Antiangiogenic therapy reverses the immunosuppressive breast cancer microenvironment.
Wuzhen Chen, Lesang Shen, +5 authors, Zhigang Chen.
Biomark Res, 2021 Jul 24; 9(1). PMID: 34294146    Free PMC article.
Review.
Novel roles of c-Met in the survival of renal cancer cells through the regulation of HO-1 and PD-L1 expression.
Murugabaskar Balan, Eduardo Mier y Teran, +4 authors, Soumitro Pal.
J Biol Chem, 2015 Feb 04; 290(13). PMID: 25645920    Free PMC article.
Expression of Vascular Endothelial Growth Factor in Ovarian Cancer Inhibits Tumor Immunity through the Accumulation of Myeloid-Derived Suppressor Cells.
Naoki Horikawa, Kaoru Abiko, +6 authors, Ikuo Konishi.
Clin Cancer Res, 2016 Jul 13; 23(2). PMID: 27401249
Highly Cited.
Immune escape to PD-L1/PD-1 blockade: seven steps to success (or failure).
J M Kim, D S Chen.
Ann Oncol, 2016 May 22; 27(8). PMID: 27207108
Highly Cited. Review.
ARCTIC: durvalumab with or without tremelimumab as third-line or later treatment of metastatic non-small-cell lung cancer.
D Planchard, N Reinmuth, +15 authors, D Kowalski.
Ann Oncol, 2020 Mar 24; 31(5). PMID: 32201234
Targeting adenosine for cancer immunotherapy.
Robert D Leone, Leisha A Emens.
J Immunother Cancer, 2018 Jun 20; 6(1). PMID: 29914571    Free PMC article.
Highly Cited. Review.
Direct and Indirect Modulation of T Cells by VEGF-A Counteracted by Anti-Angiogenic Treatment.
Morgane Bourhis, Juliette Palle, Isabelle Galy-Fauroux, Magali Terme.
Front Immunol, 2021 Apr 16; 12. PMID: 33854498    Free PMC article.
Review.
Angiopoietin-2 regulates gene expression in TIE2-expressing monocytes and augments their inherent proangiogenic functions.
Seth B Coffelt, Andrea O Tal, +8 authors, Claire E Lewis.
Cancer Res, 2010 Jun 10; 70(13). PMID: 20530679
Highly Cited.
TIGIT/CD155 blockade enhances anti-PD-L1 therapy in head and neck squamous cell carcinoma by targeting myeloid-derived suppressor cells.
Liang Mao, Yao Xiao, +3 authors, Zhi-Jun Sun.
Oral Oncol, 2021 Aug 02; 121. PMID: 34333450
Camrelizumab plus carboplatin and pemetrexed versus chemotherapy alone in chemotherapy-naive patients with advanced non-squamous non-small-cell lung cancer (CameL): a randomised, open-label, multicentre, phase 3 trial.
Caicun Zhou, Gongyan Chen, +34 authors, CameL Study Group.
Lancet Respir Med, 2020 Dec 22; 9(3). PMID: 33347829
MAHOGANY: margetuximab combination in HER2+ unresectable/metastatic gastric/gastroesophageal junction adenocarcinoma.
Daniel Vt Catenacci, Minori Rosales, +4 authors, Yoon-Koo Kang.
Future Oncol, 2020 Dec 03; 17(10). PMID: 33263418
Severe immune-related adverse events are common with sequential PD-(L)1 blockade and osimertinib.
A J Schoenfeld, K C Arbour, +7 authors, M D Hellmann.
Ann Oncol, 2019 Mar 09; 30(5). PMID: 30847464    Free PMC article.
Development and Preliminary Clinical Activity of PD-1-Guided CTLA-4 Blocking Bispecific DART Molecule.
Alexey Berezhnoy, Bradley J Sumrow, +16 authors, Paul A Moore.
Cell Rep Med, 2020 Dec 31; 1(9). PMID: 33377134    Free PMC article.
Combined Blockade of IL6 and PD-1/PD-L1 Signaling Abrogates Mutual Regulation of Their Immunosuppressive Effects in the Tumor Microenvironment.
Hirotake Tsukamoto, Koji Fujieda, +7 authors, Hiroyuki Oshiumi.
Cancer Res, 2018 Jul 04; 78(17). PMID: 29967259
Highly Cited.
Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial.
Peter Schmid, Hope S Rugo, +13 authors, IMpassion130 Investigators.
Lancet Oncol, 2019 Dec 02; 21(1). PMID: 31786121
Highly Cited.
Phase I Trial of M7824 (MSB0011359C), a Bifunctional Fusion Protein Targeting PD-L1 and TGFβ, in Advanced Solid Tumors.
Julius Strauss, Christopher R Heery, +12 authors, James L Gulley.
Clin Cancer Res, 2018 Jan 05; 24(6). PMID: 29298798    Free PMC article.
Highly Cited.
Camrelizumab Plus Apatinib in Patients With Advanced Cervical Cancer (CLAP): A Multicenter, Open-Label, Single-Arm, Phase II Trial.
Chunyan Lan, Jingxian Shen, +15 authors, Xin Huang.
J Clin Oncol, 2020 Oct 15; 38(34). PMID: 33052760    Free PMC article.
The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma.
Lars Ny, Henrik Jespersen, +15 authors, Jonas A Nilsson.
Nat Commun, 2021 Aug 29; 12(1). PMID: 34453044    Free PMC article.
cGAS-STING, an important pathway in cancer immunotherapy.
Minlin Jiang, Peixin Chen, +8 authors, Caicun Zhou.
J Hematol Oncol, 2020 Jun 24; 13(1). PMID: 32571374    Free PMC article.
Review.
Chimeric antigen receptor T cells: a novel therapy for solid tumors.
Shengnan Yu, Anping Li, +4 authors, Kongming Wu.
J Hematol Oncol, 2017 Mar 31; 10(1). PMID: 28356156    Free PMC article.
Highly Cited. Review.
Manipulating Gut Microbiota Composition to Enhance the Therapeutic Effect of Cancer Immunotherapy.
Ming Yi, Dechao Jiao, +3 authors, Kongming Wu.
Integr Cancer Ther, 2019 Sep 14; 18. PMID: 31517538    Free PMC article.
Review.
Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study.
Jong-Mu Sun, Lin Shen, +23 authors, KEYNOTE-590 Investigators.
Lancet, 2021 Aug 30; 398(10302). PMID: 34454674
Nivolumab Plus Erlotinib in Patients With EGFR-Mutant Advanced NSCLC.
Scott Gettinger, Matthew D Hellmann, +12 authors, Naiyer Rizvi.
J Thorac Oncol, 2018 May 29; 13(9). PMID: 29802888
A novel bispecific nanobody with PD-L1/TIGIT dual immune checkpoint blockade.
Linlin Ma, Junwei Gai, +5 authors, Yakun Wan.
Biochem Biophys Res Commun, 2020 Aug 13; 531(2). PMID: 32782142
Type I interferons induced by radiation therapy mediate recruitment and effector function of CD8(+) T cells.
Joanne Y H Lim, Scott A Gerber, Shawn P Murphy, Edith M Lord.
Cancer Immunol Immunother, 2013 Dec 21; 63(3). PMID: 24357146    Free PMC article.
Tyrosine phosphatase SHP2 inhibitors in tumor-targeted therapies.
Zhendong Song, Meijing Wang, +4 authors, Xiao-Feng Xiong.
Acta Pharm Sin B, 2021 Feb 04; 11(1). PMID: 33532178    Free PMC article.
Review.
Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an open-label, single-arm, phase 2 study.
Marina Chiara Garassino, Byoung-Chul Cho, +16 authors, ATLANTIC Investigators.
Lancet Oncol, 2018 Mar 17; 19(4). PMID: 29545095    Free PMC article.
Highly Cited.
Metronomic chemotherapy with low-dose cyclophosphamide plus gemcitabine can induce anti-tumor T cell immunity in vivo.
Miki Tongu, Nanae Harashima, +4 authors, Mamoru Harada.
Cancer Immunol Immunother, 2012 Aug 29; 62(2). PMID: 22926062
The Folate Pathway Inhibitor Pemetrexed Pleiotropically Enhances Effects of Cancer Immunotherapy.
David A Schaer, Sandaruwan Geeganage, +24 authors, Ruslan D Novosiadly.
Clin Cancer Res, 2019 Aug 15; 25(23). PMID: 31409612
Gemcitabine nanoparticles promote antitumor immunity against melanoma.
Yuan Zhang, Xin Bush, Bingfang Yan, Justin A Chen.
Biomaterials, 2018 Nov 06; 189. PMID: 30388589    Free PMC article.
Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer.
Martin Reck, Delvys Rodríguez-Abreu, +16 authors, KEYNOTE-024 Investigators.
N Engl J Med, 2016 Oct 11; 375(19). PMID: 27718847
Highly Cited.
Molecular characterization of ALK, a receptor tyrosine kinase expressed specifically in the nervous system.
T Iwahara, J Fujimoto, +6 authors, T Yamamoto.
Oncogene, 1997 Jan 30; 14(4). PMID: 9053841
Highly Cited.
Immunogenic cell death in cancer therapy.
Guido Kroemer, Lorenzo Galluzzi, Oliver Kepp, Laurence Zitvogel.
Annu Rev Immunol, 2012 Nov 20; 31. PMID: 23157435
Highly Cited. Review.
TGFβ drives immune evasion in genetically reconstituted colon cancer metastasis.
Daniele V F Tauriello, Sergio Palomo-Ponce, +15 authors, Eduard Batlle.
Nature, 2018 Feb 15; 554(7693). PMID: 29443964
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Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial.
F Stephen Hodi, Jason Chesney, +18 authors, Michael A Postow.
Lancet Oncol, 2016 Sep 14; 17(11). PMID: 27622997    Free PMC article.
Highly Cited.
The PD1:PD-L1/2 Pathway from Discovery to Clinical Implementation.
Kankana Bardhan, Theodora Anagnostou, Vassiliki A Boussiotis.
Front Immunol, 2016 Dec 27; 7. PMID: 28018338    Free PMC article.
Highly Cited. Review.
EGFR-TKIs resistance via EGFR-independent signaling pathways.
Qian Liu, Shengnan Yu, +3 authors, Kongming Wu.
Mol Cancer, 2018 Feb 20; 17(1). PMID: 29455669    Free PMC article.
Highly Cited. Review.
Impact of 5-Fu/oxaliplatin on mouse dendritic cells and synergetic effect with a colon cancer vaccine.
Xinqiang Hong, Tiangeng Dong, +4 authors, Weixin Niu.
Chin J Cancer Res, 2018 Jun 05; 30(2). PMID: 29861605    Free PMC article.
Generation and Characterization of a Bispecific Antibody Targeting Both PD-1 and c-MET.
Yi Wu, Min Yu, +4 authors, Wei Mo.
Protein Pept Lett, 2017 Oct 20; 24(12). PMID: 29046141
Blockade of checkpoint receptor PVRIG unleashes anti-tumor immunity of NK cells in murine and human solid tumors.
Yangyang Li, Yu Zhang, +7 authors, Haoyu Sun.
J Hematol Oncol, 2021 Jun 28; 14(1). PMID: 34174928    Free PMC article.
PD-1 suppresses TCR-CD8 cooperativity during T-cell antigen recognition.
Kaitao Li, Zhou Yuan, +4 authors, Cheng Zhu.
Nat Commun, 2021 May 14; 12(1). PMID: 33980853    Free PMC article.
LAG-3 and PD-1+LAG-3 inhibition promote anti-tumor immune responses in human autologous melanoma/T cell co-cultures.
Nicolas Gestermann, Damien Saugy, +6 authors, Grégory Verdeil.
Oncoimmunology, 2020 Aug 28; 9(1). PMID: 32850194    Free PMC article.
Making the first move in EGFR-driven or ALK-driven NSCLC: first-generation or next-generation TKI?
Gonzalo Recondo, Francesco Facchinetti, +2 authors, Luc Friboulet.
Nat Rev Clin Oncol, 2018 Aug 16; 15(11). PMID: 30108370
Highly Cited. Review.
Pembrolizumab Plus Pegylated Interferon alfa-2b or Ipilimumab for Advanced Melanoma or Renal Cell Carcinoma: Dose-Finding Results from the Phase Ib KEYNOTE-029 Study.
Michael B Atkins, F Stephen Hodi, +14 authors, Antoni Ribas.
Clin Cancer Res, 2018 Jan 24; 24(8). PMID: 29358500
Suppression of Type I IFN Signaling in Tumors Mediates Resistance to Anti-PD-1 Treatment That Can Be Overcome by Radiotherapy.
Xiaohong Wang, Jonathan E Schoenhals, +18 authors, James W Welsh.
Cancer Res, 2016 Nov 09; 77(4). PMID: 27821490    Free PMC article.
Highly Cited.
Cancer immunotherapy using anti-TIM3/PD-1 bispecific antibody: a patent evaluation of EP3356411A1.
Irma Herrera-Camacho, Maricruz Anaya-Ruiz, +3 authors, Gerardo Landeta.
Expert Opin Ther Pat, 2019 Jun 27; 29(8). PMID: 31241380
Review.
Cancer-associated adipocytes as immunomodulators in cancer.
Qi Wu, Bei Li, +3 authors, Shengrong Sun.
Biomark Res, 2021 Jan 09; 9(1). PMID: 33413697    Free PMC article.
Review.
PD-L1 is a novel direct target of HIF-1α, and its blockade under hypoxia enhanced MDSC-mediated T cell activation.
Muhammad Zaeem Noman, Giacomo Desantis, +5 authors, Salem Chouaib.
J Exp Med, 2014 Apr 30; 211(5). PMID: 24778419    Free PMC article.
Highly Cited.
Safety of combining radiotherapy with immune-checkpoint inhibition.
William L Hwang, Luke R G Pike, +2 authors, Jay S Loeffler.
Nat Rev Clin Oncol, 2018 Jun 07; 15(8). PMID: 29872177
Highly Cited. Review.
Avelumab plus standard-of-care chemoradiotherapy versus chemoradiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial.
Nancy Y Lee, Robert L Ferris, +18 authors, Ezra Cohen.
Lancet Oncol, 2021 Apr 02; 22(4). PMID: 33794205
Single-Arm Phases 1 and 2 Trial of Niraparib in Combination With Pembrolizumab in Patients With Recurrent Platinum-Resistant Ovarian Carcinoma.
Panagiotis A Konstantinopoulos, Steven Waggoner, +22 authors, Pamela Munster.
JAMA Oncol, 2019 Jun 14; 5(8). PMID: 31194228    Free PMC article.
Highly Cited.
Safety and Antitumor Activity of α-PD-L1 Antibody as Monotherapy or in Combination with α-TIM-3 Antibody in Patients with Microsatellite Instability-High/Mismatch Repair-Deficient Tumors.
Antoine Hollebecque, Hyun C Chung, +17 authors, Yung-Jue Bang.
Clin Cancer Res, 2021 Sep 02; 27(23). PMID: 34465599
A Phase II Study of Pembrolizumab in EGFR-Mutant, PD-L1+, Tyrosine Kinase Inhibitor Naïve Patients With Advanced NSCLC.
A Lisberg, A Cummings, +23 authors, Edward B Garon.
J Thorac Oncol, 2018 Jun 07; 13(8). PMID: 29874546    Free PMC article.
Highly Cited.
Combined VEGFR and CTLA-4 blockade increases the antigen-presenting function of intratumoral DCs and reduces the suppressive capacity of intratumoral MDSCs.
Stephanie Du Four, Sarah K Maenhout, +3 authors, Joeri L Aerts.
Am J Cancer Res, 2016 Dec 03; 6(11). PMID: 27904768    Free PMC article.
Low-dose cyclophosphamide depletes circulating naïve and activated regulatory T cells in malignant pleural mesothelioma patients synergistically treated with dendritic cell-based immunotherapy.
Lisanne Noordam, Margaretha E H Kaijen, +7 authors, Heleen Vroman.
Oncoimmunology, 2018 Dec 14; 7(12). PMID: 30524884    Free PMC article.
A Dual-Bioresponsive Drug-Delivery Depot for Combination of Epigenetic Modulation and Immune Checkpoint Blockade.
Huitong Ruan, Quanyin Hu, +7 authors, Zhen Gu.
Adv Mater, 2019 Mar 12; 31(17). PMID: 30856290
TATTON: a multi-arm, phase Ib trial of osimertinib combined with selumetinib, savolitinib, or durvalumab in EGFR-mutant lung cancer.
G R Oxnard, J C-H Yang, +12 authors, M-J Ahn.
Ann Oncol, 2020 Mar 07; 31(4). PMID: 32139298
Clinical development of the anti-CTLA-4 antibody tremelimumab.
Antoni Ribas.
Semin Oncol, 2010 Nov 16; 37(5). PMID: 21074059
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Recent advances of highly selective CDK4/6 inhibitors in breast cancer.
Hanxiao Xu, Shengnan Yu, +4 authors, Kongming Wu.
J Hematol Oncol, 2017 Apr 26; 10(1). PMID: 28438180    Free PMC article.
Highly Cited. Review.
Blocking TGF-β Signaling To Enhance The Efficacy Of Immune Checkpoint Inhibitor.
Xianguang Bai, Ming Yi, +2 authors, Kongming Wu.
Onco Targets Ther, 2019 Dec 07; 12. PMID: 31807028    Free PMC article.
Review.
Phase 1/2 Study of the Safety and Tolerability of Nivolumab Plus Crizotinib for the First-Line Treatment of Anaplastic Lymphoma Kinase Translocation - Positive Advanced Non-Small Cell Lung Cancer (CheckMate 370).
David R Spigel, Craig Reynolds, +9 authors, George Blumenschein.
J Thorac Oncol, 2018 Mar 09; 13(5). PMID: 29518553
Highly Cited.
Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice.
Liufu Deng, Hua Liang, +4 authors, Yang-Xin Fu.
J Clin Invest, 2014 Jan 03; 124(2). PMID: 24382348    Free PMC article.
Highly Cited.
Immune modulatory effects of oncogenic KRAS in cancer.
Shaima'a Hamarsheh, Olaf Groß, Tilman Brummer, Robert Zeiser.
Nat Commun, 2020 Oct 30; 11(1). PMID: 33116132    Free PMC article.
Review.
Phase Ib Study of Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Combination with Pembrolizumab (MK-3475) in Patients with Advanced Solid Tumors.
Anthony W Tolcher, Mario Sznol, +11 authors, Laura Q M Chow.
Clin Cancer Res, 2017 Jun 22; 23(18). PMID: 28634283
Highly Cited.
Phase Ib study of atezolizumab combined with cobimetinib in patients with solid tumors.
M D Hellmann, T-W Kim, +18 authors, J Bendell.
Ann Oncol, 2019 Mar 29; 30(7). PMID: 30918950    Free PMC article.
Adenosine 2A Receptor Blockade as an Immunotherapy for Treatment-Refractory Renal Cell Cancer.
Lawrence Fong, Andrew Hotson, +30 authors, Richard A Miller.
Cancer Discov, 2019 Nov 17; 10(1). PMID: 31732494    Free PMC article.
Small molecule AZD4635 inhibitor of A2AR signaling rescues immune cell function including CD103+ dendritic cells enhancing anti-tumor immunity.
Alexandra Borodovsky, Christine M Barbon, +21 authors, Deanna A Mele.
J Immunother Cancer, 2020 Jul 31; 8(2). PMID: 32727810    Free PMC article.
Manganese enhances the antitumor function of CD8+ T cells by inducing type I interferon production.
Yuan Song, Yonghao Liu, +7 authors, Haiyan Liu.
Cell Mol Immunol, 2020 Aug 18; 18(6). PMID: 32801367    Free PMC article.
Entinostat induces antitumor immune responses through immune editing of tumor neoantigens.
Andrew S Truong, Mi Zhou, +14 authors, William Y Kim.
J Clin Invest, 2021 Aug 17; 131(16). PMID: 34396985    Free PMC article.
Synergistic effect of immune checkpoint blockade and anti-angiogenesis in cancer treatment.
Ming Yi, Dechao Jiao, +3 authors, Anping Li.
Mol Cancer, 2019 Mar 31; 18(1). PMID: 30925919    Free PMC article.
Highly Cited. Review.
The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity.
Chen Zhu, Ana C Anderson, +6 authors, Vijay K Kuchroo.
Nat Immunol, 2005 Nov 16; 6(12). PMID: 16286920
Highly Cited.
Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Second-Line Treatment of Patients With NSCLC: Results From an Expansion Cohort of a Phase 1 Trial.
Luis Paz-Ares, Tae Min Kim, +12 authors, Byoung Chul Cho.
J Thorac Oncol, 2020 Mar 17; 15(7). PMID: 32173464    Free PMC article.
Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer.
Michael J Overman, Sara Lonardi, +17 authors, Thierry André.
J Clin Oncol, 2018 Jan 23; 36(8). PMID: 29355075
Highly Cited.
Next-generation immuno-oncology agents: current momentum shifts in cancer immunotherapy.
Chongxian Pan, Hongtao Liu, +4 authors, Lei Zheng.
J Hematol Oncol, 2020 Apr 05; 13(1). PMID: 32245497    Free PMC article.
Review.
STING and the innate immune response to nucleic acids in the cytosol.
Dara L Burdette, Russell E Vance.
Nat Immunol, 2012 Dec 15; 14(1). PMID: 23238760
Highly Cited. Review.
Safety and clinical activity with an anti-PD-1 antibody JS001 in advanced melanoma or urologic cancer patients.
Bixia Tang, Xieqiao Yan, +20 authors, Jun Guo.
J Hematol Oncol, 2019 Jan 16; 12(1). PMID: 30642373    Free PMC article.
Highly Cited.
ICOS agonism by JTX-2011 (vopratelimab) requires initial T cell priming and Fc cross-linking for optimal T cell activation and anti-tumor immunity in preclinical models.
Amanda Hanson, Kutlu Elpek, +16 authors, Christopher J Harvey.
PLoS One, 2020 Sep 25; 15(9). PMID: 32970735    Free PMC article.
An epigenetically altered tumor cell vaccine.
A Nazmul H Khan, William J Magner, Thomas B Tomasi.
Cancer Immunol Immunother, 2004 Mar 05; 53(8). PMID: 14997346
Consecutive low doses of cyclophosphamide preferentially target Tregs and potentiate T cell responses induced by DNA PLG microparticle immunization.
Christine M Barbon, Min Yang, +4 authors, Thomas M Luby.
Cell Immunol, 2010 Mar 09; 262(2). PMID: 20206921
Cyclic [G(2',5')pA(3',5')p] is the metazoan second messenger produced by DNA-activated cyclic GMP-AMP synthase.
Pu Gao, Manuel Ascano, +9 authors, Dinshaw J Patel.
Cell, 2013 May 08; 153(5). PMID: 23647843    Free PMC article.
Highly Cited.
Cancer-associated fibroblasts: an emerging target of anti-cancer immunotherapy.
Tongyan Liu, Chencheng Han, +4 authors, Rong Yin.
J Hematol Oncol, 2019 Aug 30; 12(1). PMID: 31462327    Free PMC article.
Highly Cited. Review.
Phase Ib Study of Crizotinib plus Pembrolizumab in Patients with Previously Untreated Advanced Non-Small Cell Lung Cancer with ALK Translocation.
Sandip Pravin Patel, Suchita Pakkala, +5 authors, Francisco Robert-Vizcarrondo.
Oncologist, 2020 Feb 13; 25(7). PMID: 32048771    Free PMC article.
Gut microbiota: Role in pathogen colonization, immune responses, and inflammatory disease.
Joseph M Pickard, Melody Y Zeng, Roberta Caruso, Gabriel Núñez.
Immunol Rev, 2017 Sep 01; 279(1). PMID: 28856738    Free PMC article.
Highly Cited. Review.
HGF/MET and the Immune System: Relevance for Cancer Immunotherapy.
Federica Papaccio, Carminia Maria Della Corte, +5 authors, Floriana Morgillo.
Int J Mol Sci, 2018 Nov 18; 19(11). PMID: 30441809    Free PMC article.
Review.
Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC.
Scott J Antonia, Augusto Villegas, +31 authors, PACIFIC Investigators.
N Engl J Med, 2018 Oct 04; 379(24). PMID: 30280658
Highly Cited.
Expression of immune checkpoints on circulating tumor cells in men with metastatic prostate cancer.
Tian Zhang, Anika Agarwal, +13 authors, Andrew J Armstrong.
Biomark Res, 2021 Feb 20; 9(1). PMID: 33602330    Free PMC article.
Combination cancer immunotherapies tailored to the tumour microenvironment.
Mark J Smyth, Shin Foong Ngiow, Antoni Ribas, Michele W L Teng.
Nat Rev Clin Oncol, 2015 Nov 26; 13(3). PMID: 26598942
Highly Cited. Review.
Recent advances of dual FGFR inhibitors as a novel therapy for cancer.
Qi Liang, Juelan Wang, +3 authors, Jianyou Shi.
Eur J Med Chem, 2021 Feb 09; 214. PMID: 33556787
Review.
Molecular mechanism of SHP2 activation by PD-1 stimulation.
M Marasco, A Berteotti, +9 authors, T Carlomagno.
Sci Adv, 2020 Feb 18; 6(5). PMID: 32064351    Free PMC article.
Type I interferon response and innate immune sensing of cancer.
Mercedes B Fuertes, Seng-Ryong Woo, +2 authors, Thomas F Gajewski.
Trends Immunol, 2012 Nov 06; 34(2). PMID: 23122052    Free PMC article.
Highly Cited. Review.
Anti-PD-1 Antibody SHR-1210 Combined with Apatinib for Advanced Hepatocellular Carcinoma, Gastric, or Esophagogastric Junction Cancer: An Open-label, Dose Escalation and Expansion Study.
Jianming Xu, Yun Zhang, +12 authors, Quanren Wang.
Clin Cancer Res, 2018 Oct 24; 25(2). PMID: 30348638
Highly Cited.
Combination of PD-1 Inhibitor and OX40 Agonist Induces Tumor Rejection and Immune Memory in Mouse Models of Pancreatic Cancer.
Ying Ma, Jun Li, +8 authors, Cassian Yee.
Gastroenterology, 2020 Mar 18; 159(1). PMID: 32179091    Free PMC article.
The Glutaminase Inhibitor CB-839 (Telaglenastat) Enhances the Antimelanoma Activity of T-Cell-Mediated Immunotherapies.
Sruthy Varghese, Snigdha Pramanik, +13 authors, Y N Vashisht Gopal.
Mol Cancer Ther, 2020 Dec 29; 20(3). PMID: 33361272    Free PMC article.
Intranasal delivery of the cytoplasmic domain of CTLA-4 using a novel protein transduction domain prevents allergic inflammation.
Je-Min Choi, Mi-Hyun Ahn, +15 authors, Sang-Kyou Lee.
Nat Med, 2006 Apr 11; 12(5). PMID: 16604087
Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma.
James Larkin, Vanna Chiarion-Sileni, +28 authors, Jedd D Wolchok.
N Engl J Med, 2019 Sep 29; 381(16). PMID: 31562797
Highly Cited.
Safety, Efficacy, and Pharmacodynamics of Tremelimumab Plus Durvalumab for Patients With Unresectable Hepatocellular Carcinoma: Randomized Expansion of a Phase I/II Study.
Robin Kate Kelley, Bruno Sangro, +21 authors, Ghassan K Abou-Alfa.
J Clin Oncol, 2021 Jul 23; 39(27). PMID: 34292792    Free PMC article.
Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma.
Richard S Finn, Shukui Qin, +19 authors, IMbrave150 Investigators.
N Engl J Med, 2020 May 14; 382(20). PMID: 32402160
The role of cancer-derived microRNAs in cancer immune escape.
Ming Yi, Linping Xu, +3 authors, Kongming Wu.
J Hematol Oncol, 2020 Mar 31; 13(1). PMID: 32222150    Free PMC article.
Review.
Systematically optimized BCMA/CS1 bispecific CAR-T cells robustly control heterogeneous multiple myeloma.
Eugenia Zah, Eunwoo Nam, +6 authors, Yvonne Y Chen.
Nat Commun, 2020 May 10; 11(1). PMID: 32385241    Free PMC article.
Mouse, but not human STING, binds and signals in response to the vascular disrupting agent 5,6-dimethylxanthenone-4-acetic acid.
Joseph Conlon, Dara L Burdette, +10 authors, Katherine A Fitzgerald.
J Immunol, 2013 Apr 16; 190(10). PMID: 23585680    Free PMC article.
Highly Cited.
Safety and Clinical Activity of Pembrolizumab and Multisite Stereotactic Body Radiotherapy in Patients With Advanced Solid Tumors.
Jason J Luke, Jeffrey M Lemons, +17 authors, Steven J Chmura.
J Clin Oncol, 2018 Feb 14; 36(16). PMID: 29437535    Free PMC article.
Highly Cited.
Abscopal effect of radiotherapy combined with immune checkpoint inhibitors.
Yang Liu, Yinping Dong, +3 authors, Jinming Yu.
J Hematol Oncol, 2018 Aug 18; 11(1). PMID: 30115069    Free PMC article.
Highly Cited. Review.
Eradication of metastatic mouse cancers resistant to immune checkpoint blockade by suppression of myeloid-derived cells.
KiBem Kim, Andrew D Skora, +8 authors, Shibin Zhou.
Proc Natl Acad Sci U S A, 2014 Jul 30; 111(32). PMID: 25071169    Free PMC article.
Highly Cited.
Durvalumab With or Without Tremelimumab vs Standard Chemotherapy in First-line Treatment of Metastatic Non-Small Cell Lung Cancer: The MYSTIC Phase 3 Randomized Clinical Trial.
Naiyer A Rizvi, Byoung Chul Cho, +28 authors, MYSTIC Investigators.
JAMA Oncol, 2020 Apr 10; 6(5). PMID: 32271377    Free PMC article.
Clinical relevance of PD-L1 expression and CD8+ T cells infiltration in patients with EGFR-mutated and ALK-rearranged lung cancer.
Si-Yang Liu, Zhong-Yi Dong, +12 authors, Yi-Long Wu.
Lung Cancer, 2018 Nov 16; 125. PMID: 30429043
The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients.
Vyara Matson, Jessica Fessler, +5 authors, Thomas F Gajewski.
Science, 2018 Jan 06; 359(6371). PMID: 29302014    Free PMC article.
Highly Cited.
Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4.
Shuang Qin, Linping Xu, +3 authors, Suxia Luo.
Mol Cancer, 2019 Nov 07; 18(1). PMID: 31690319    Free PMC article.
Highly Cited. Review.
Engineering a Smart Agent for Enhanced Immunotherapy Effect by Simultaneously Blocking PD-L1 and CTLA-4.
Chunjuan Jiang, Le Zhang, +5 authors, Shaoli Song.
Adv Sci (Weinh), 2021 Sep 03; 8(20). PMID: 34473430    Free PMC article.
Increased Hepatotoxicity Associated with Sequential Immune Checkpoint Inhibitor and Crizotinib Therapy in Patients with Non-Small Cell Lung Cancer.
Jessica J Lin, Emily Chin, +8 authors, Alice T Shaw.
J Thorac Oncol, 2018 Sep 12; 14(1). PMID: 30205166    Free PMC article.
Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy.
Ayelet Sivan, Leticia Corrales, +9 authors, Thomas F Gajewski.
Science, 2015 Nov 07; 350(6264). PMID: 26541606    Free PMC article.
Highly Cited.
PD-1 Blockade and CD27 Stimulation Activate Distinct Transcriptional Programs That Synergize for CD8+ T-Cell-Driven Antitumor Immunity.
Sarah L Buchan, Mohannad Fallatah, +8 authors, Aymen Al-Shamkhani.
Clin Cancer Res, 2018 Mar 09; 24(10). PMID: 29514845    Free PMC article.
CDK4/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation.
Jiehui Deng, Eric S Wang, +44 authors, Kwok-Kin Wong.
Cancer Discov, 2017 Nov 05; 8(2). PMID: 29101163    Free PMC article.
Highly Cited.
Cyclophosphamide synergizes with type I interferons through systemic dendritic cell reactivation and induction of immunogenic tumor apoptosis.
Giovanna Schiavoni, Antonella Sistigu, +10 authors, Laura Bracci.
Cancer Res, 2010 Dec 16; 71(3). PMID: 21156650
Highly Cited.
Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.
V Gopalakrishnan, C N Spencer, +67 authors, J A Wargo.
Science, 2017 Nov 04; 359(6371). PMID: 29097493    Free PMC article.
Highly Cited.
Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients.
Diwakar Davar, Amiran K Dzutsev, +29 authors, Hassane M Zarour.
Science, 2021 Feb 06; 371(6529). PMID: 33542131    Free PMC article.
Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study.
Jedd D Wolchok, Bart Neyns, +14 authors, Celeste Lebbé.
Lancet Oncol, 2009 Dec 17; 11(2). PMID: 20004617
Highly Cited.
5-Fluorouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity.
Julie Vincent, Grégoire Mignot, +7 authors, François Ghiringhelli.
Cancer Res, 2010 Apr 15; 70(8). PMID: 20388795
Highly Cited.
Development of PARP and Immune-Checkpoint Inhibitor Combinations.
Ross A Stewart, Patrick G Pilié, Timothy A Yap.
Cancer Res, 2018 Dec 01; 78(24). PMID: 30498083
Review.
Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial.
Luis Paz-Ares, Mikhail Dvorkin, +22 authors, CASPIAN investigators.
Lancet, 2019 Oct 09; 394(10212). PMID: 31590988
Highly Cited.
CTLA-4: new insights into its biological function and use in tumor immunotherapy.
Jackson G Egen, Michael S Kuhns, James P Allison.
Nat Immunol, 2002 Jun 28; 3(7). PMID: 12087419
Highly Cited. Review.
Radiotherapy and anti-PD-1/PD-L1 combinations in lung cancer: building better translational research platforms.
T Kordbacheh, J Honeychurch, +2 authors, T Illidge.
Ann Oncol, 2018 Jan 09; 29(2). PMID: 29309540
Review.
FGFR-TKI resistance in cancer: current status and perspectives.
Sitong Yue, Yukun Li, +4 authors, Daichao Wu.
J Hematol Oncol, 2021 Feb 12; 14(1). PMID: 33568192    Free PMC article.
Review.
Circulating myeloid-derived suppressor cells increase in patients undergoing neo-adjuvant chemotherapy for breast cancer.
Robert Wesolowski, Megan C Duggan, +15 authors, William E Carson.
Cancer Immunol Immunother, 2017 Jul 09; 66(11). PMID: 28688082    Free PMC article.
CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms.
Richard V Parry, Jens M Chemnitz, +6 authors, James L Riley.
Mol Cell Biol, 2005 Oct 18; 25(21). PMID: 16227604    Free PMC article.
Highly Cited.
The construction, expression, and enhanced anti-tumor activity of YM101: a bispecific antibody simultaneously targeting TGF-β and PD-L1.
Ming Yi, Jing Zhang, +6 authors, Kongming Wu.
J Hematol Oncol, 2021 Feb 18; 14(1). PMID: 33593403    Free PMC article.
A novel tetravalent bispecific antibody targeting programmed death 1 and tyrosine-protein kinase Met for treatment of gastric cancer.
Weihua Hou, Qingyun Yuan, +4 authors, Min Yu.
Invest New Drugs, 2018 Dec 05; 37(5). PMID: 30511201
Immune-Related Adverse Events Associated with Immune Checkpoint Blockade.
Michael A Postow, Robert Sidlow, Matthew D Hellmann.
N Engl J Med, 2018 Jan 11; 378(2). PMID: 29320654
Highly Cited. Review.
Tumor-selective blockade of CD47 signaling with a CD47/PD-L1 bispecific antibody for enhanced anti-tumor activity and limited toxicity.
Yan Wang, Haiqing Ni, +15 authors, Junjian Liu.
Cancer Immunol Immunother, 2020 Aug 08; 70(2). PMID: 32761423
Co-stimulatory agonists: An insight into the immunotherapy of cancer.
Ramin Pourakbari, Farnaz Hajizadeh, +3 authors, Leili Aghebati-Maleki.
EXCLI J, 2021 Jul 17; 20. PMID: 34267616    Free PMC article.
Review.
Ipilimumab-dependent cell-mediated cytotoxicity of regulatory T cells ex vivo by nonclassical monocytes in melanoma patients.
Emanuela Romano, Monika Kusio-Kobialka, +7 authors, Daniel E Speiser.
Proc Natl Acad Sci U S A, 2015 Apr 29; 112(19). PMID: 25918390    Free PMC article.
Highly Cited.
Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study.
Corey J Langer, Shirish M Gadgeel, +17 authors, KEYNOTE-021 investigators.
Lancet Oncol, 2016 Oct 18; 17(11). PMID: 27745820    Free PMC article.
Highly Cited.
Novel therapies emerging in oncology to target the TGF-β pathway.
Byung-Gyu Kim, Ehsan Malek, +2 authors, James J Driscoll.
J Hematol Oncol, 2021 Apr 08; 14(1). PMID: 33823905    Free PMC article.
Review.
Advances and perspectives of PARP inhibitors.
Ming Yi, Bing Dong, +3 authors, Suxia Luo.
Exp Hematol Oncol, 2019 Nov 19; 8. PMID: 31737426    Free PMC article.
Review.
Cytokines in Cancer Immunotherapy.
Thomas A Waldmann.
Cold Spring Harb Perspect Biol, 2017 Nov 05; 10(12). PMID: 29101107    Free PMC article.
Highly Cited. Review.
STING agonist loaded lipid nanoparticles overcome anti-PD-1 resistance in melanoma lung metastasis via NK cell activation.
Takashi Nakamura, Takanori Sato, +6 authors, Hideyoshi Harashima.
J Immunother Cancer, 2021 Jul 04; 9(7). PMID: 34215690    Free PMC article.
Efficacy and safety of camrelizumab combined with apatinib in advanced triple-negative breast cancer: an open-label phase II trial.
Jieqiong Liu, Qiang Liu, +10 authors, Erwei Song.
J Immunother Cancer, 2020 May 26; 8(1). PMID: 32448804    Free PMC article.
Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial.
Vicky Makker, Drew Rasco, +13 authors, Matthew Taylor.
Lancet Oncol, 2019 Mar 30; 20(5). PMID: 30922731
Highly Cited.
Efficacy and Safety of Nivolumab Plus Ipilimumab in Patients With Advanced Hepatocellular Carcinoma Previously Treated With Sorafenib: The CheckMate 040 Randomized Clinical Trial.
Thomas Yau, Yoon-Koo Kang, +18 authors, Chiun Hsu.
JAMA Oncol, 2020 Oct 02; 6(11). PMID: 33001135    Free PMC article.
Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer.
Christina Twyman-Saint Victor, Andrew J Rech, +22 authors, Andy J Minn.
Nature, 2015 Mar 11; 520(7547). PMID: 25754329    Free PMC article.
Highly Cited.
Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma.
James Larkin, Vanna Chiarion-Sileni, +28 authors, Jedd D Wolchok.
N Engl J Med, 2015 Jun 02; 373(1). PMID: 26027431    Free PMC article.
Highly Cited.
PEGylated IL-10 (Pegilodecakin) Induces Systemic Immune Activation, CD8+ T Cell Invigoration and Polyclonal T Cell Expansion in Cancer Patients.
Aung Naing, Jeffrey R Infante, +21 authors, Martin Oft.
Cancer Cell, 2018 Nov 14; 34(5). PMID: 30423297    Free PMC article.
Synthetic Lethality in Ovarian Cancer.
Akshaya Chandrasekaran, Kevin M Elias.
Mol Cancer Ther, 2021 Sep 15; 20(11). PMID: 34518297    Free PMC article.
Review.
Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer.
Matthew D Hellmann, Luis Paz-Ares, +23 authors, Suresh S Ramalingam.
N Engl J Med, 2019 Sep 29; 381(21). PMID: 31562796
Highly Cited.
Safety and Efficacy of Durvalumab With or Without Tremelimumab in Patients With PD-L1-Low/Negative Recurrent or Metastatic HNSCC: The Phase 2 CONDOR Randomized Clinical Trial.
Lillian L Siu, Caroline Even, +18 authors, Jérôme Fayette.
JAMA Oncol, 2018 Nov 02; 5(2). PMID: 30383184    Free PMC article.
Highly Cited.
The CDK4/6 Inhibitor Abemaciclib Induces a T Cell Inflamed Tumor Microenvironment and Enhances the Efficacy of PD-L1 Checkpoint Blockade.
David A Schaer, Richard P Beckmann, +19 authors, Michael Kalos.
Cell Rep, 2018 Mar 15; 22(11). PMID: 29539425
Highly Cited.
Applications of gut microbiota in patients with hematopoietic stem-cell transplantation.
Jifeng Yu, Hao Sun, +4 authors, Zhongxing Jiang.
Exp Hematol Oncol, 2020 Dec 10; 9(1). PMID: 33292670    Free PMC article.
Review.
Tumor angiogenesis.
Robert S Kerbel.
N Engl J Med, 2008 May 09; 358(19). PMID: 18463380    Free PMC article.
Highly Cited. Review.
The epigenetic immunomodulator, HBI-8000, enhances the response and reverses resistance to checkpoint inhibitors.
Reid P Bissonnette, Rosemary M Cesario, +2 authors, Mireille Gillings.
BMC Cancer, 2021 Sep 01; 21(1). PMID: 34461854    Free PMC article.
Development of bispecific anti-c-Met/PD-1 diabodies for the treatment of solid tumors and the effect of c-Met binding affinity on efficacy.
Qingyun Yuan, Qiaoyan Liang, +5 authors, Min Yu.
Oncoimmunology, 2021 Aug 06; 10(1). PMID: 34350059    Free PMC article.
Role of the cGAS-STING pathway in cancer development and oncotherapeutic approaches.
Li Teng Khoo, Liuh-Yow Chen.
EMBO Rep, 2018 Nov 18; 19(12). PMID: 30446584    Free PMC article.
Review.
Dual targeting strategies with bispecific antibodies.
Roland E Kontermann.
MAbs, 2012 Mar 29; 4(2). PMID: 22453100    Free PMC article.
Highly Cited. Review.
Combination cancer immunotherapy targeting PD-1 and GITR can rescue CD8.
Bei Wang, Wen Zhang, +21 authors, Dimitris Skokos.
Sci Immunol, 2018 Nov 06; 3(29). PMID: 30389797
Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer.
Leena Gandhi, Delvys Rodríguez-Abreu, +27 authors, KEYNOTE-189 Investigators.
N Engl J Med, 2018 Apr 17; 378(22). PMID: 29658856
Highly Cited.
Blocking TIM-3 in Treatment-refractory Advanced Solid Tumors: A Phase Ia/b Study of LY3321367 with or without an Anti-PD-L1 Antibody.
James J Harding, Victor Moreno, +16 authors, Maria J de Miguel.
Clin Cancer Res, 2021 Jan 31; 27(8). PMID: 33514524
Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): a multicentre, randomised, open-label, phase 3 trial.
Howard West, Michael McCleod, +17 authors, Federico Cappuzzo.
Lancet Oncol, 2019 May 28; 20(7). PMID: 31122901
Highly Cited.
Avelumab plus axitinib versus sunitinib in advanced renal cell carcinoma: biomarker analysis of the phase 3 JAVELIN Renal 101 trial.
Robert J Motzer, Paul B Robbins, +20 authors, Toni K Choueiri.
Nat Med, 2020 Sep 09; 26(11). PMID: 32895571    Free PMC article.
Dual angiopoietin-2 and VEGFA inhibition elicits antitumor immunity that is enhanced by PD-1 checkpoint blockade.
Martina Schmittnaegel, Nicolò Rigamonti, +8 authors, Michele De Palma.
Sci Transl Med, 2017 Apr 14; 9(385). PMID: 28404865
Highly Cited.
Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2.
Tadashi Yokosuka, Masako Takamatsu, +3 authors, Takashi Saito.
J Exp Med, 2012 May 30; 209(6). PMID: 22641383    Free PMC article.
Highly Cited.
Bempegaldesleukin (NKTR-214) plus Nivolumab in Patients with Advanced Solid Tumors: Phase I Dose-Escalation Study of Safety, Efficacy, and Immune Activation (PIVOT-02).
Adi Diab, Nizar M Tannir, +20 authors, Daniel C Cho.
Cancer Discov, 2020 May 23; 10(8). PMID: 32439653
Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open-label, phase 3 trial.
Thomas Powles, Elizabeth R Plimack, +17 authors, Brian I Rini.
Lancet Oncol, 2020 Dec 08; 21(12). PMID: 33284113
Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma.
Tyler R Simpson, Fubin Li, +11 authors, Sergio A Quezada.
J Exp Med, 2013 Jul 31; 210(9). PMID: 23897981    Free PMC article.
Highly Cited.
PARP Inhibitor Efficacy Depends on CD8+ T-cell Recruitment via Intratumoral STING Pathway Activation in BRCA-Deficient Models of Triple-Negative Breast Cancer.
Constantia Pantelidou, Olmo Sonzogni, +14 authors, Geoffrey I Shapiro.
Cancer Discov, 2019 Apr 25; 9(6). PMID: 31015319    Free PMC article.
Highly Cited.
Oncology meets immunology: the cancer-immunity cycle.
Daniel S Chen, Ira Mellman.
Immunity, 2013 Jul 31; 39(1). PMID: 23890059
Highly Cited. Review.
Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors.
Bertrand Routy, Emmanuelle Le Chatelier, +45 authors, Laurence Zitvogel.
Science, 2017 Nov 04; 359(6371). PMID: 29097494
Highly Cited.
The Intersection between Tumor Angiogenesis and Immune Suppression.
Osama E Rahma, F Stephen Hodi.
Clin Cancer Res, 2019 Apr 05; 25(18). PMID: 30944124
Review.
Safety and Efficacy of Durvalumab and Tremelimumab Alone or in Combination in Patients with Advanced Gastric and Gastroesophageal Junction Adenocarcinoma.
Ronan J Kelly, Jeeyun Lee, +21 authors, Geoffrey Y Ku.
Clin Cancer Res, 2019 Nov 05; 26(4). PMID: 31676670    Free PMC article.
RAS-targeted therapies: is the undruggable drugged?
Amanda R Moore, Scott C Rosenberg, Frank McCormick, Shiva Malek.
Nat Rev Drug Discov, 2020 Jun 13; 19(8). PMID: 32528145    Free PMC article.
Review.
Distinct Roles of VEGFA and ANGPT2 in Lung Adenocarcinoma and Squamous Cell Carcinoma.
Shuang Qin, Ming Yi, +2 authors, Kongming Wu.
J Cancer, 2020 Jan 02; 11(1). PMID: 31892982    Free PMC article.
First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer.
Leora Horn, Aaron S Mansfield, +19 authors, IMpower133 Study Group.
N Engl J Med, 2018 Oct 04; 379(23). PMID: 30280641
Highly Cited.
The efficacy and safety of combination of PD-1 and CTLA-4 inhibitors: a meta-analysis.
Kongju Wu, Ming Yi, +3 authors, Kongming Wu.
Exp Hematol Oncol, 2019 Nov 02; 8. PMID: 31673481    Free PMC article.
Review.
Stereotactic body radiotherapy for oligometastases.
Alison C Tree, Vincent S Khoo, +7 authors, Nicholas J van As.
Lancet Oncol, 2013 Jan 02; 14(1). PMID: 23276369
Highly Cited. Review.
CTLA-4 (CD152): A versatile receptor for immune-based therapy.
Holger Lingel, Monika C Brunner-Weinzierl.
Semin Immunol, 2019 Oct 13; 42. PMID: 31604536
Review.
Elements of cancer immunity and the cancer-immune set point.
Daniel S Chen, Ira Mellman.
Nature, 2017 Jan 20; 541(7637). PMID: 28102259
Highly Cited. Review.
Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial.
Jonathan W Goldman, Mikhail Dvorkin, +23 authors, CASPIAN investigators.
Lancet Oncol, 2020 Dec 08; 22(1). PMID: 33285097
A human CD137×PD-L1 bispecific antibody promotes anti-tumor immunity via context-dependent T cell costimulation and checkpoint blockade.
Cecile Geuijen, Paul Tacken, +38 authors, Mark Throsby.
Nat Commun, 2021 Jul 23; 12(1). PMID: 34290245    Free PMC article.
Immunotherapies targeting stimulatory pathways and beyond.
Julian A Marin-Acevedo, ErinMarie O Kimbrough, +2 authors, Yanyan Lou.
J Hematol Oncol, 2021 May 14; 14(1). PMID: 33980266    Free PMC article.
Review.
A Phase I Study of APX005M and Cabiralizumab with or without Nivolumab in Patients with Melanoma, Kidney Cancer, or Non-Small Cell Lung Cancer Resistant to Anti-PD-1/PD-L1.
Sarah A Weiss, Dijana Djureinovic, +19 authors, Harriet M Kluger.
Clin Cancer Res, 2021 Jun 19; 27(17). PMID: 34140403
Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study.
Zhenggang Ren, Jianming Xu, +38 authors, ORIENT-32 study group.
Lancet Oncol, 2021 Jun 19; 22(7). PMID: 34143971
Pembrolizumab versus Ipilimumab in Advanced Melanoma.
Caroline Robert, Jacob Schachter, +20 authors, KEYNOTE-006 investigators.
N Engl J Med, 2015 Apr 22; 372(26). PMID: 25891173
Highly Cited.
Phase II Trial of IL-12 Plasmid Transfection and PD-1 Blockade in Immunologically Quiescent Melanoma.
Alain P Algazi, Christopher G Twitty, +21 authors, Adil I Daud.
Clin Cancer Res, 2020 May 08; 26(12). PMID: 32376655
RAS/MAPK Activation Is Associated with Reduced Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors.
Sherene Loi, Sathana Dushyanthen, +22 authors, Justin M Balko.
Clin Cancer Res, 2015 Oct 31; 22(6). PMID: 26515496    Free PMC article.
Highly Cited.
Oxaliplatin induces immunogenic cell death in hepatocellular carcinoma cells and synergizes with immune checkpoint blockade therapy.
Hanzhang Zhu, Yuqiang Shan, +3 authors, Changku Jia.
Cell Oncol (Dordr), 2020 Aug 17; 43(6). PMID: 32797385
An orally available non-nucleotide STING agonist with antitumor activity.
Bo-Sheng Pan, Samanthi A Perera, +38 authors, George H Addona.
Science, 2020 Aug 21; 369(6506). PMID: 32820094
Gene modification strategies for next-generation CAR T cells against solid cancers.
Yonggui Tian, Yilu Li, Yupei Shao, Yi Zhang.
J Hematol Oncol, 2020 May 20; 13(1). PMID: 32423475    Free PMC article.
Review.
Blockade of mutant RAS oncogenic signaling with a special emphasis on KRAS.
Robert Roskoski.
Pharmacol Res, 2021 Aug 28; 172. PMID: 34450320
Review.
Phase 1b Study of Sintilimab Plus Anlotinib as First-line Therapy in Patients With Advanced NSCLC.
Tianqing Chu, Runbo Zhong, +16 authors, Baohui Han.
J Thorac Oncol, 2021 Feb 02; 16(4). PMID: 33524601
Combination strategies to maximize the benefits of cancer immunotherapy.
Shaoming Zhu, Tian Zhang, +5 authors, Chong-Xian Pan.
J Hematol Oncol, 2021 Sep 29; 14(1). PMID: 34579759    Free PMC article.
Review.
MET-Oncogenic and JAK2-Inactivating Alterations Are Independent Factors That Affect Regulation of PD-L1 Expression in Lung Cancer.
Maria Saigi, Juan J Alburquerque-Bejar, +8 authors, Montse Sanchez-Cespedes.
Clin Cancer Res, 2018 Jun 15; 24(18). PMID: 29898990
HDAC Inhibition Upregulates PD-1 Ligands in Melanoma and Augments Immunotherapy with PD-1 Blockade.
David M Woods, Andressa L Sodré, +3 authors, Jeffrey Weber.
Cancer Immunol Res, 2015 Aug 25; 3(12). PMID: 26297712    Free PMC article.
Highly Cited.
Dual PD-L1 and TGF-b blockade in patients with recurrent respiratory papillomatosis.
Yvette Robbins, Jay Friedman, +10 authors, Scott Norberg.
J Immunother Cancer, 2021 Sep 01; 9(8). PMID: 34462327    Free PMC article.
Blocking siglec-10hi tumor-associated macrophages improves anti-tumor immunity and enhances immunotherapy for hepatocellular carcinoma.
Nan Xiao, Xiaodong Zhu, +6 authors, Hui-Chuan Sun.
Exp Hematol Oncol, 2021 Jun 12; 10(1). PMID: 34112250    Free PMC article.
Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity.
Kaori Sakuishi, Lionel Apetoh, +3 authors, Ana C Anderson.
J Exp Med, 2010 Sep 08; 207(10). PMID: 20819927    Free PMC article.
Highly Cited.
The biology of combination immunotherapy in recurrent metastatic head and neck cancer.
Xun Yuan, Ming Yi, +4 authors, Kongming Wu.
Int J Biochem Cell Biol, 2021 May 08; 136. PMID: 33962022
Review.
Phase 1/2 Trial of Pembrolizumab and Concurrent Chemoradiation Therapy for Limited-Stage SCLC.
James W Welsh, John V Heymach, +21 authors, Bonnie Glisson.
J Thorac Oncol, 2020 Sep 12; 15(12). PMID: 32916308
An Open-label Randomized Phase 2 study of Durvalumab Alone or in Combination with Tremelimumab in Patients with Advanced Germ Cell Tumors (APACHE): Results from the First Planned Interim Analysis.
Andrea Necchi, Patrizia Giannatempo, +9 authors, Roberto Salvioni.
Eur Urol, 2018 Sep 24; 75(1). PMID: 30243800
Double-edged roles of protein tyrosine phosphatase SHP2 in cancer and its inhibitors in clinical trials.
Yihui Song, Min Zhao, Huiqing Zhang, Bin Yu.
Pharmacol Ther, 2021 Aug 18; 230. PMID: 34403682
Review.
Combined antitumor effects of anti-EGFR variant III CAR-T cell therapy and PD-1 checkpoint blockade on glioblastoma in mouse model.
Yujie Song, Qingtian Liu, +2 authors, Shunchang Jiao.
Cell Immunol, 2020 Apr 20; 352. PMID: 32305131
Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial.
Robert J Motzer, Brian I Rini, +36 authors, CheckMate 214 investigators.
Lancet Oncol, 2019 Aug 21; 20(10). PMID: 31427204    Free PMC article.
Highly Cited.
Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4.
Omar S Qureshi, Yong Zheng, +12 authors, David M Sansom.
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Combination Immunotherapy with CAR T Cells and Checkpoint Blockade for the Treatment of Solid Tumors.
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Combination therapy with PD-1/PD-L1 blockade in non-small cell lung cancer: strategies and mechanisms.
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A2A Adenosine Receptor Gene Deletion or Synthetic A2A Antagonist Liberate Tumor-Reactive CD8+ T Cells from Tumor-Induced Immunosuppression.
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J Immunol, 2011 Mar 04; 186(7). PMID: 21368233
Tislelizumab Plus Chemotherapy as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC (RATIONALE 304): A Randomized Phase 3 Trial.
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Axitinib in Combination With Toripalimab, a Humanized Immunoglobulin G4 Monoclonal Antibody Against Programmed Cell Death-1, in Patients With Metastatic Mucosal Melanoma: An Open-Label Phase IB Trial.
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Gut microbiome modulates efficacy of immune checkpoint inhibitors.
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Camrelizumab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (CAPTAIN-1st): a multicentre, randomised, double-blind, phase 3 trial.
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Pamiparib in combination with tislelizumab in patients with advanced solid tumours: results from the dose-escalation stage of a multicentre, open-label, phase 1a/b trial.
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Immune Checkpoint Inhibitors in EGFR-Mutated NSCLC: Dusk or Dawn?
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Lancet Oncol, 2019 Apr 21; 20(6). PMID: 31003911
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Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial.
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Genetic Aberrations in the CDK4 Pathway Are Associated with Innate Resistance to PD-1 Blockade in Chinese Patients with Non-Cutaneous Melanoma.
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Targeting PD-1/PD-L1 pathway in myelodysplastic syndromes and acute myeloid leukemia.
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Cross-talk between HIF and PD-1/PD-L1 pathways in carcinogenesis and therapy.
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