Journal Article
. 2014 Dec; 194(3):950-9.
doi: 10.4049/jimmunol.1401686.

Combination therapy with anti-CTLA-4 and anti-PD-1 leads to distinct immunologic changes in vivo

Rituparna Das 1 Rakesh Verma 1 Mario Sznol 1 Chandra Sekhar Boddupalli 1 Scott N Gettinger 1 Harriet Kluger 1 Margaret Callahan 2 Jedd D Wolchok 2 Ruth Halaban 3 Madhav V Dhodapkar 1 Kavita M Dhodapkar 4 
  • PMID: 25539810
  •     40 References
  •     190 citations


Combination therapy concurrently targeting PD-1 and CTLA-4 immune checkpoints leads to remarkable antitumor effects. Although both PD-1 and CTLA-4 dampen the T cell activation, the in vivo effects of these drugs in humans remain to be clearly defined. To better understand biologic effects of therapy, we analyzed blood/tumor tissue from 45 patients undergoing single or combination immune checkpoint blockade. We show that blockade of CTLA-4, PD-1, or combination of the two leads to distinct genomic and functional signatures in vivo in purified human T cells and monocytes. Therapy-induced changes are more prominent in T cells than in monocytes and involve largely nonoverlapping changes in coding genes, including alternatively spliced transcripts and noncoding RNAs. Pathway analysis revealed that CTLA-4 blockade induces a proliferative signature predominantly in a subset of transitional memory T cells, whereas PD-1 blockade instead leads to changes in genes implicated in cytolysis and NK cell function. Combination blockade leads to nonoverlapping changes in gene expression, including proliferation-associated and chemokine genes. These therapies also have differential effects on plasma levels of CXCL10, soluble IL-2R, and IL-1α. Importantly, PD-1 receptor occupancy following anti-PD-1 therapy may be incomplete in the tumor T cells even in the setting of complete receptor occupancy in circulating T cells. These data demonstrate that, despite shared property of checkpoint blockade, Abs against PD-1, CTLA-4 alone, or in combination have distinct immunologic effects in vivo. Improved understanding of pharmacodynamic effects of these agents in patients will support rational development of immune-based combinations against cancer.

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Rituparna Das, Noffar Bar, +10 authors, Kavita M Dhodapkar.
J Clin Invest, 2018 Jan 09; 128(2). PMID: 29309048    Free PMC article.
Highly Cited.
B cells as biomarkers: predicting immune checkpoint therapy adverse events.
Shannon M Liudahl, Lisa M Coussens.
J Clin Invest, 2018 Jan 09; 128(2). PMID: 29309049    Free PMC article.
New Strategies Using Antibody Combinations to Increase Cancer Treatment Effectiveness.
Isabel Corraliza-Gorjón, Beatriz Somovilla-Crespo, +2 authors, Leonor Kremer.
Front Immunol, 2018 Jan 10; 8. PMID: 29312320    Free PMC article.
Anti-PD-1/anti-CTLA-4 efficacy in melanoma brain metastases depends on extracranial disease and augmentation of CD8+ T cell trafficking.
David Taggart, Tereza Andreou, +7 authors, Mihaela Lorger.
Proc Natl Acad Sci U S A, 2018 Feb 02; 115(7). PMID: 29386395    Free PMC article.
Highly Cited.
New horizons from immunotherapy in malignant pleural mesothelioma.
Luana Calabrò, Giulia Rossi, Michele Maio.
J Thorac Dis, 2018 Mar 07; 10(Suppl 2). PMID: 29507802    Free PMC article.
Putting the brakes on CTLA-4 inhibition in lung cancer?
Meghan J Mooradian, Justin F Gainor.
Transl Lung Cancer Res, 2018 Mar 14; 7(Suppl 1). PMID: 29531902    Free PMC article.
Toxicological and pharmacological assessment of AGEN1884, a novel human IgG1 anti-CTLA-4 antibody.
Randi B Gombos, Ana Gonzalez, +24 authors, Nicholas S Wilson.
PLoS One, 2018 Apr 05; 13(4). PMID: 29617360    Free PMC article.
Novel Systemic Therapies for Advanced Gastric Cancer.
Hong Jun Kim, Sang Cheul Oh.
J Gastric Cancer, 2018 Apr 10; 18(1). PMID: 29629216    Free PMC article.
Discovery and preclinical characterization of the antagonist anti-PD-L1 monoclonal antibody LY3300054.
Yiwen Li, Carmine Carpenito, +18 authors, Michael Kalos.
J Immunother Cancer, 2018 May 02; 6(1). PMID: 29712568    Free PMC article.
Programmed cell death-1 and programmed cell death ligand-1 antibodies-induced dysthyroidism.
Jaafar Jaafar, Eugenio Fernandez, Heba Alwan, Jacques Philippe.
Endocr Connect, 2018 May 10; 7(5). PMID: 29739808    Free PMC article.
Melanoma Immunotherapy: Next-Generation Biomarkers.
Sabrina A Hogan, Mitchell P Levesque, Phil F Cheng.
Front Oncol, 2018 Jun 14; 8. PMID: 29896449    Free PMC article.
Shining light on advanced NSCLC in 2017: combining immune checkpoint inhibitors.
Meng Qiao, Tao Jiang, Caicun Zhou.
J Thorac Dis, 2018 Jun 29; 10(Suppl 13). PMID: 29951304    Free PMC article.
Urothelial bladder cancer may suppress perforin expression in CD8+ T cells by an ICAM-1/TGFβ2 mediated pathway.
Ciputra Adijaya Hartana, Emma Ahlén Bergman, +10 authors, Ola Winqvist.
PLoS One, 2018 Jul 03; 13(7). PMID: 29966014    Free PMC article.
Resistance to Systemic Therapies in Clear Cell Renal Cell Carcinoma: Mechanisms and Management Strategies.
Peter Makhov, Shreyas Joshi, +3 authors, Vladimir M Kolenko.
Mol Cancer Ther, 2018 Jul 04; 17(7). PMID: 29967214    Free PMC article.
Role of Tissue-Resident Memory in Intra-Tumor Heterogeneity and Response to Immune Checkpoint Blockade.
Kavita M Dhodapkar.
Front Immunol, 2018 Aug 01; 9. PMID: 30061902    Free PMC article.
Cancer Stem Cell Vaccination With PD-L1 and CTLA-4 Blockades Enhances the Eradication of Melanoma Stem Cells in a Mouse Tumor Model.
Fang Zheng, Jianzhong Dang, +7 authors, Qiao Li.
J Immunother, 2018 Aug 01; 41(8). PMID: 30063587    Free PMC article.
Targeting Checkpoint Receptors and Molecules for Therapeutic Modulation of Natural Killer Cells.
Nayoung Kim, Hun Sik Kim.
Front Immunol, 2018 Sep 27; 9. PMID: 30250471    Free PMC article.
Highly Cited. Review.
Combination of immune checkpoint blockade with DNA cancer vaccine induces potent antitumor immunity against P815 mastocytoma.
Alessandra Lopes, Kevin Vanvarenberg, +5 authors, Gaëlle Vandermeulen.
Sci Rep, 2018 Oct 26; 8(1). PMID: 30356111    Free PMC article.
The efficacy and safety of immune checkpoint inhibitor combination therapy in lung cancer: a systematic review and meta-analysis.
Min Peng, Xing Li, +3 authors, Qi Bin Song.
Onco Targets Ther, 2018 Nov 15; 11. PMID: 30425525    Free PMC article.
Crosstalk Between PD-1/PD-L1 Blockade and Its Combinatorial Therapies in Tumor Immune Microenvironment: A Focus on HNSCC.
Weimin Lin, Miao Chen, +2 authors, Qianming Chen.
Front Oncol, 2018 Dec 07; 8. PMID: 30519541    Free PMC article.
BRAF and MEK inhibitors differentially affect nivolumab-induced T cell activation by modulating the TCR and AKT signaling pathways.
Peng Yue, Taylor Harper, +6 authors, Gerald M Feldman.
Oncoimmunology, 2018 Dec 14; 8(1). PMID: 30546949    Free PMC article.
Clonal Deletion of Tumor-Specific T Cells by Interferon-γ Confers Therapeutic Resistance to Combination Immune Checkpoint Blockade.
Chien-Chun Steven Pai, John T Huang, +24 authors, Lawrence Fong.
Immunity, 2019 Feb 10; 50(2). PMID: 30737146    Free PMC article.
Highly Cited.
Targeting immune cells for cancer therapy.
Sin Yee Gun, Sharon Wei Ling Lee, Je Lin Sieow, Siew Cheng Wong.
Redox Biol, 2019 Mar 29; 25. PMID: 30917934    Free PMC article.
Highly Cited. Review.
Safety of Nivolumab plus Low-Dose Ipilimumab in Previously Treated Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer.
Michael A Morse, Michael J Overman, +7 authors, Bassel El-Rayes.
Oncologist, 2019 May 31; 24(11). PMID: 31147488    Free PMC article.
Circulating biomarkers predictive of tumor response to cancer immunotherapy.
Ernest Y Lee, Rajan P Kulkarni.
Expert Rev Mol Diagn, 2019 Aug 31; 19(10). PMID: 31469965    Free PMC article.
Endocrine-related adverse events associated with immune-checkpoint inhibitors in patients with melanoma.
Eva Kassi, Anna Angelousi, +10 authors, Helen Gogas.
Cancer Med, 2019 Sep 14; 8(15). PMID: 31518074    Free PMC article.
Combination anti-CTLA-4 plus anti-PD-1 checkpoint blockade utilizes cellular mechanisms partially distinct from monotherapies.
Spencer C Wei, Nana-Ama A S Anang, +8 authors, James P Allison.
Proc Natl Acad Sci U S A, 2019 Oct 23; 116(45). PMID: 31636208    Free PMC article.
Comprehensive immune profiling and immune-monitoring using body fluid of patients with metastatic gastric cancer.
Hyung Soon Park, Woo Sun Kwon, +11 authors, Sun Young Rha.
J Immunother Cancer, 2019 Oct 23; 7(1). PMID: 31639056    Free PMC article.
Targeting the Immune Microenvironment in the Treatment of Head and Neck Squamous Cell Carcinoma.
Hui-Ching Wang, Leong-Perng Chan, Shih-Feng Cho.
Front Oncol, 2019 Nov 05; 9. PMID: 31681613    Free PMC article.
Small molecules as theranostic agents in cancer immunology.
Jindian Li, Juno Van Valkenburgh, +3 authors, Kai Chen.
Theranostics, 2019 Nov 07; 9(25). PMID: 31695804    Free PMC article.
Immunotherapy of Hepatocellular Carcinoma with Magnetic PD-1 Peptide-Imprinted Polymer Nanocomposite and Natural Killer Cells.
Mei-Hwa Lee, Kai-Hsi Liu, +2 authors, Hung-Yin Lin.
Biomolecules, 2019 Nov 17; 9(11). PMID: 31731492    Free PMC article.
Perspectives on Treatment of Metastatic Colorectal Cancer with Immune Checkpoint Inhibitor Therapy.
Michael A Morse, Howard Hochster, Al Benson.
Oncologist, 2019 Aug 07; 25(1). PMID: 31383813    Free PMC article.
Lessons learned from the blockade of immune checkpoints in cancer immunotherapy.
Xiaolei Li, Changshun Shao, Yufang Shi, Weidong Han.
J Hematol Oncol, 2018 Feb 28; 11(1). PMID: 29482595    Free PMC article.
Highly Cited. Review.
Sensitizing the Tumor Microenvironment to Immune Checkpoint Therapy.
Rachael M Zemek, Wee Loong Chin, +3 authors, W Joost Lesterhuis.
Front Immunol, 2020 Mar 07; 11. PMID: 32133005    Free PMC article.
Computational Immune Monitoring Reveals Abnormal Double-Negative T Cells Present across Human Tumor Types.
Allison R Greenplate, Daniel D McClanahan, +12 authors, Jonathan M Irish.
Cancer Immunol Res, 2018 Nov 11; 7(1). PMID: 30413431    Free PMC article.
Checkpoint Blockade Immunotherapy Induces Dynamic Changes in PD-1-CD8+ Tumor-Infiltrating T Cells.
Sema Kurtulus, Asaf Madi, +10 authors, Ana C Anderson.
Immunity, 2019 Jan 13; 50(1). PMID: 30635236    Free PMC article.
Highly Cited.
Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001.
O Hamid, C Robert, +17 authors, A Ribas.
Ann Oncol, 2019 Feb 05; 30(4). PMID: 30715153    Free PMC article.
Highly Cited.
Clinical outcomes of advanced stage cancer patients treated with sequential immunotherapy in phase 1 clinical trials.
Dylan J Martini, Yuan Liu, +19 authors, Mehmet Asim Bilen.
Invest New Drugs, 2019 Feb 07; 37(6). PMID: 30725388    Free PMC article.
Ubiquitin Ligases in Cancer Immunotherapy - Balancing Antitumor and Autoimmunity.
Yu Fujita, Roberto Tinoco, +2 authors, Ze'ev A Ronai.
Trends Mol Med, 2019 Mar 23; 25(5). PMID: 30898473    Free PMC article.
Fatal myocarditis and rhabdomyositis in a patient with stage IV melanoma treated with combined ipilimumab and nivolumab.
S D Saibil, L Bonilla, +5 authors, M O Butler.
Curr Oncol, 2019 Jul 10; 26(3). PMID: 31285688    Free PMC article.
Dissecting the Role of the FGF19-FGFR4 Signaling Pathway in Cancer Development and Progression.
Yanan Liu, Meng Cao, +3 authors, Ri Cui.
Front Cell Dev Biol, 2020 Mar 11; 8. PMID: 32154250    Free PMC article.
Determinants of Resistance to Checkpoint Inhibitors.
Linda Tran, Dan Theodorescu.
Int J Mol Sci, 2020 Mar 01; 21(5). PMID: 32111080    Free PMC article.
Anti-PD-1 monoclonal antibody MEDI0680 in a phase I study of patients with advanced solid malignancies.
Aung Naing, Jeffrey Infante, +18 authors, Michael Oberst.
J Immunother Cancer, 2019 Aug 24; 7(1). PMID: 31439037    Free PMC article.
Combination immunotherapy with anti-PD-L1 antibody and depletion of regulatory T cells during acute viral infections results in improved virus control but lethal immunopathology.
Paul David, Malgorzata Drabczyk-Pluta, +24 authors, Gennadiy Zelinskyy.
PLoS Pathog, 2020 Apr 01; 16(3). PMID: 32226027    Free PMC article.
Immune microenvironment modulation unmasks therapeutic benefit of radiotherapy and checkpoint inhibition.
Jared M Newton, Aurelie Hanoteau, +11 authors, Andrew G Sikora.
J Immunother Cancer, 2019 Aug 15; 7(1). PMID: 31409394    Free PMC article.
A good start of immunotherapy in esophageal cancer.
Qian Zhao, Jinming Yu, Xue Meng.
Cancer Med, 2019 Jun 25; 8(10). PMID: 31231980    Free PMC article.
Adverse Events Following Cancer Immunotherapy: Obstacles and Opportunities.
Kristen E Pauken, Michael Dougan, +2 authors, Arlene H Sharpe.
Trends Immunol, 2019 May 06; 40(6). PMID: 31053497    Free PMC article.
Highly Cited. Review.
Approach to the Patient with Recurrent/Metastatic Disease.
Joël Guigay, Esma Sâada-Bouzid, Frédéric Peyrade, Cécile Michel.
Curr Treat Options Oncol, 2019 Jun 27; 20(8). PMID: 31240480
Immune Checkpoint Inhibition in Sepsis: A Phase 1b Randomized, Placebo-Controlled, Single Ascending Dose Study of Antiprogrammed Cell Death-Ligand 1 Antibody (BMS-936559).
Richard S Hotchkiss, Elizabeth Colston, +12 authors, Dennis M Grasela.
Crit Care Med, 2019 Feb 13; 47(5). PMID: 30747773    Free PMC article.
Highly Cited.
Tumor microenvironmental influences on dendritic cell and T cell function: A focus on clinically relevant immunologic and metabolic checkpoints.
Kristian M Hargadon.
Clin Transl Med, 2020 Jun 09; 10(1). PMID: 32508018    Free PMC article.
Biomarkers for immunotherapy for treatment of glioblastoma.
John P Lynes, Anthony K Nwankwo, +5 authors, Edjah K Nduom.
J Immunother Cancer, 2020 Jun 01; 8(1). PMID: 32474411    Free PMC article.
Plasma Cells in the Melanoma Tumor Microenvironment-Mechanistic Roles for IgA.
Rakesh Verma, Lalit Kumar.
Front Immunol, 2020 Jun 26; 11. PMID: 32582154    Free PMC article.
Immunological Targets for Immunotherapy: Inhibitory T Cell Receptors.
Diwakar Davar, Hassane M Zarour.
Methods Mol Biol, 2019 Sep 11; 2055. PMID: 31502146    Free PMC article.
Durvalumab and tremelimumab combination therapy versus durvalumab or tremelimumab monotherapy for patients with solid tumors: A systematic review and meta-analysis.
Bi-Cheng Wang, Peng-Cheng Li, +2 authors, Quentin Liu.
Medicine (Baltimore), 2020 Jul 16; 99(28). PMID: 32664183    Free PMC article.
Systematic Review.
Differential effects of PD-L1 versus PD-1 blockade on myeloid inflammation in human cancer.
Noffar Bar, Federica Costa, +19 authors, Madhav V Dhodapkar.
JCI Insight, 2020 May 20; 5(12). PMID: 32427579    Free PMC article.
Subtype and grade-dependent spatial heterogeneity of T-cell infiltration in pediatric glioma.
M Hope Robinson, Juan Vasquez, +4 authors, Kavita Dhodapkar.
J Immunother Cancer, 2020 Aug 14; 8(2). PMID: 32788236    Free PMC article.
Immune-Driven Pathogenesis of Neurotoxicity after Exposure of Cancer Patients to Immune Checkpoint Inhibitors.
Noelia Vilariño, Jordi Bruna, +2 authors, Andreas A Argyriou.
Int J Mol Sci, 2020 Aug 17; 21(16). PMID: 32796758    Free PMC article.
Biomarkers of immunotherapy in non-small cell lung cancer.
Lingling Wang, Yue Hu, +2 authors, Xiaochen Wang.
Oncol Lett, 2020 Sep 17; 20(5). PMID: 32934707    Free PMC article.
Salvage Ipilimumab and Nivolumab in Patients With Metastatic Renal Cell Carcinoma After Prior Immune Checkpoint Inhibitors.
Anita Gul, Tyler F Stewart, +10 authors, Brian I Rini.
J Clin Oncol, 2020 Jun 04; 38(27). PMID: 32491962    Free PMC article.
Checkpoint inhibition of PD-L1 and CTLA-4 in a child with refractory acute leukemia.
Larisa Broglie, Jill Gershan, Michael J Burke.
Int J Hematol Oncol, 2019 Mar 14; 8(1). PMID: 30863527    Free PMC article.
Immune mechanisms of idiosyncratic drug-induced liver injury.
Alastair Mak, Jack Uetrecht.
J Clin Transl Res, 2017 Feb 12; 3(1). PMID: 30873473    Free PMC article.
Nivolumab plus ipilimumab combination therapy for the first-line treatment NSCLC: evidence to date.
Jordi Remon, Laura Esteller, Álvaro Taus.
Cancer Manag Res, 2019 Jun 20; 11. PMID: 31213908    Free PMC article.
Management of pembrolizumab-induced steroid refractory mucositis with infliximab: A case report.
Harry Dang, Jiyuan Sun, +3 authors, Jaffar Hilli.
World J Clin Cases, 2020 Oct 08; 8(18). PMID: 33024767    Free PMC article.
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.
Combination therapy: Future directions of immunotherapy in small cell lung cancer.
Wei Huang, Jia-Jia Chen, Rui Xing, Yue-Can Zeng.
Transl Oncol, 2020 Oct 17; 14(1). PMID: 33065386    Free PMC article.
Targeting Innate Immunity to Treat Cancer.
Matthew Austin, Harriet Kluger.
Cancers (Basel), 2020 Sep 27; 12(10). PMID: 32977403    Free PMC article.
Efficacy of nivolumab and ipilimumab in patients with malignant pleural mesothelioma is related to a subtype of effector memory cytotoxic T cells: Translational evidence from two clinical trials.
Joanne M Mankor, Maria J Disselhorst, +3 authors, Heleen Vroman.
EBioMedicine, 2020 Nov 10; 62. PMID: 33166791    Free PMC article.
Agnostic evaluation of ipilimumab and nivolumab association: a metanalysis.
Paolo Marchetti, Andrea Botticelli, +2 authors, Diana Giannarelli.
J Transl Med, 2020 Nov 27; 18(1). PMID: 33239030    Free PMC article.
A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization.
Miguel F Sanmamed, Lieping Chen.
Cell, 2018 Oct 06; 175(2). PMID: 30290139    Free PMC article.
Highly Cited. Review.
Sites of metastasis and association with clinical outcome in advanced stage cancer patients treated with immunotherapy.
Mehmet Asim Bilen, Julie M Shabto, +17 authors, R Donald Harvey.
BMC Cancer, 2019 Aug 30; 19(1). PMID: 31464611    Free PMC article.
Final analysis of a phase II study of nivolumab in combination with ipilimumab for unresectable chemotherapy-naive advanced melanoma.
Kenjiro Namikawa, Yoshio Kiyohara, +10 authors, Naoya Yamazaki.
J Dermatol, 2020 Aug 20; 47(11). PMID: 32812243    Free PMC article.
Overcoming Immune Evasion in Melanoma.
Kevinn Eddy, Suzie Chen.
Int J Mol Sci, 2020 Dec 02; 21(23). PMID: 33256089    Free PMC article.
SITC cancer immunotherapy resource document: a compass in the land of biomarker discovery.
Siwen Hu-Lieskovan, Srabani Bhaumik, +14 authors, Holden T Maecker.
J Immunother Cancer, 2020 Dec 04; 8(2). PMID: 33268350    Free PMC article.
Efficacy of pembrolizumab for advanced/metastatic melanoma: a meta-analysis.
Qi Zhang, Geng-Wei Huo, Hong-Zhen Zhang, Ying Song.
Open Med (Wars), 2020 Dec 15; 15(1). PMID: 33313405    Free PMC article.
Prognostic value of intratumoral lymphocyte-to-monocyte ratio and M0 macrophage enrichment in tumor immune microenvironment of melanoma.
Neil K Jairath, Mark W Farha, +3 authors, Trilokraj Tejasvi.
Melanoma Manag, 2020 Dec 16; 7(4). PMID: 33318782    Free PMC article.
Combined immune checkpoint blockade increases CD8+CD28+PD-1+ effector T cells and provides a therapeutic strategy for patients with neuroblastoma.
Soheila Shirinbak, Randall Y Chan, +11 authors, Shahab Asgharzadeh.
Oncoimmunology, 2021 Jan 26; 10(1). PMID: 33489468    Free PMC article.
Complete response of hereditary leiomyomatosis and renal cell cancer (HLRCC)-associated renal cell carcinoma to nivolumab and ipilimumab combination immunotherapy by: a case report.
Yasuhiro Iribe, Mitsuko Furuya, +12 authors, Noboru Nakaigawa.
Fam Cancer, 2020 Jul 16; 20(1). PMID: 32666341
Peri-tumor administration of controlled release anti-CTLA-4 synergizes with systemic anti-PD-1 to induce systemic antitumor immunity while sparing autoimmune toxicity.
Airi Harui, Sandra M McLachlan, +2 authors, Michael D Roth.
Cancer Immunol Immunother, 2020 Apr 26; 69(9). PMID: 32333082
Model Informed Dosing Regimen and Phase I Results of the Anti-PD-1 Antibody Budigalimab (ABBV-181).
John Powderly, Alexander Spira, +19 authors, Anthony Tolcher.
Clin Transl Sci, 2020 Aug 10; 14(1). PMID: 32770720    Free PMC article.
Ipilimumab and nivolumab/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors.
Jeffrey Sum Lung Wong, Gerry Gin Wai Kwok, +9 authors, Thomas Yau.
J Immunother Cancer, 2021 Feb 11; 9(2). PMID: 33563773    Free PMC article.
Emerging dynamics pathways of response and resistance to PD-1 and CTLA-4 blockade: tackling uncertainty by confronting complexity.
Allan Relecom, Maysaloun Merhi, +4 authors, Said Dermime.
J Exp Clin Cancer Res, 2021 Feb 20; 40(1). PMID: 33602280    Free PMC article.
The current landscape of single-cell transcriptomics for cancer immunotherapy.
Puneeth Guruprasad, Yong Gu Lee, Ki Hyun Kim, Marco Ruella.
J Exp Med, 2021 Feb 19; 218(1). PMID: 33601414    Free PMC article.
Combination of a T cell activating therapy and anti-phosphatidylserine enhances anti-tumour immune responses in a HPV16 E7-expressing C3 tumour model.
Brennan S Dirk, Genevieve Weir, +2 authors, Marianne M Stanford.
Sci Rep, 2021 Feb 26; 11(1). PMID: 33627686    Free PMC article.
CD25-Treg-depleting antibodies preserving IL-2 signaling on effector T cells enhance effector activation and antitumor immunity.
Isabelle Solomon, Maria Amann, +29 authors, Sergio A Quezada.
Nat Cancer, 2021 Mar 02; 1(12). PMID: 33644766    Free PMC article.
Immunotyping and Quantification of Melanoma Tumor-Infiltrating Lymphocytes.
Max O Meneveau, Zeyad T Sahli, +2 authors, Craig L Slingluff.
Methods Mol Biol, 2021 Mar 12; 2265. PMID: 33704737
A Prospective, Phase 1 Trial of Nivolumab, Ipilimumab, and Radiotherapy in Patients with Advanced Melanoma.
Michael A Postow, Susan J Knox, +22 authors, Christopher A Barker.
Clin Cancer Res, 2020 Mar 25; 26(13). PMID: 32205463    Free PMC article.
Autoimmune complications of cancer immunotherapy.
Kavita M Dhodapkar.
Curr Opin Immunol, 2019 Sep 27; 61. PMID: 31557690    Free PMC article.
Bilateral murine tumor models for characterizing the response to immune checkpoint blockade.
Rachael M Zemek, Vanessa S Fear, +9 authors, W Joost Lesterhuis.
Nat Protoc, 2020 Apr 03; 15(5). PMID: 32238953
Challenges and perspectives for immunotherapy in oesophageal cancer: A look to the future (Review).
Andrea Lampis, Margherita Ratti, +4 authors, Jens Claus Hahne.
Int J Mol Med, 2021 Apr 14; 47(6). PMID: 33846775    Free PMC article.
Neoadjuvant immunotherapy for non-small cell lung cancer: State of the art.
Jin Kang, Chao Zhang, Wen-Zhao Zhong.
Cancer Commun (Lond), 2021 Mar 11; 41(4). PMID: 33689225    Free PMC article.
Cancer Vaccines, Adjuvants, and Delivery Systems.
Samantha J Paston, Victoria A Brentville, Peter Symonds, Lindy G Durrant.
Front Immunol, 2021 Apr 17; 12. PMID: 33859638    Free PMC article.
Nivolumab and Ipilimumab as Maintenance Therapy in Extensive-Disease Small-Cell Lung Cancer: CheckMate 451.
Taofeek K Owonikoko, Keunchil Park, +22 authors, Hye Ryun Kim.
J Clin Oncol, 2021 Mar 09; 39(12). PMID: 33683919    Free PMC article.
Epigenomics and immunotherapeutic advances in pediatric brain tumors.
Malak Abedalthagafi, Nahla Mobark, May Al-Rashed, Musa AlHarbi.
NPJ Precis Oncol, 2021 May 02; 5(1). PMID: 33931704    Free PMC article.
Recent Advances and Future Prospects in Immune Checkpoint (ICI)-Based Combination Therapy for Advanced HCC.
Yawen Dong, Jeffrey Sum Lung Wong, +7 authors, Thomas Yau.
Cancers (Basel), 2021 May 01; 13(8). PMID: 33919570    Free PMC article.
Modulation of the immune microenvironment of high-risk ductal carcinoma in situ by intralesional pembrolizumab injection.
Alexa C Glencer, Jasmine M Wong, +7 authors, Michael J Campbell.
NPJ Breast Cancer, 2021 May 27; 7(1). PMID: 34035311    Free PMC article.
Not-so-opposite ends of the spectrum: CD8+ T cell dysfunction across chronic infection, cancer and autoimmunity.
Jenna L Collier, Sarah A Weiss, +2 authors, Arlene H Sharpe.
Nat Immunol, 2021 Jun 19; 22(7). PMID: 34140679
Peripheral CD8+ T cell characteristics associated with durable responses to immune checkpoint blockade in patients with metastatic melanoma.
Benjamin P Fairfax, Chelsea A Taylor, +12 authors, Mark R Middleton.
Nat Med, 2020 Feb 12; 26(2). PMID: 32042196    Free PMC article.
Selecting the optimal immunotherapy regimen in driver-negative metastatic NSCLC.
Michael J Grant, Roy S Herbst, Sarah B Goldberg.
Nat Rev Clin Oncol, 2021 Jun 26; 18(10). PMID: 34168333
First-in-human phase 1 study of budigalimab, an anti-PD-1 inhibitor, in patients with non-small cell lung cancer and head and neck squamous cell carcinoma.
Antoine Italiano, Philippe A Cassier, +18 authors, Victor Moreno.
Cancer Immunol Immunother, 2021 Jul 04; 71(2). PMID: 34216247    Free PMC article.
FDA Approval Summary: Nivolumab with Ipilimumab and Chemotherapy for Metastatic Non-small Cell Lung Cancer, A Collaborative Project Orbis Review.
Paz J Vellanki, Flora Mulkey, +16 authors, Harpreet Singh.
Clin Cancer Res, 2021 Feb 27; 27(13). PMID: 33632925    Free PMC article.
Two Complementarity Immunotherapeutics in Non-Small-Cell Lung Cancer Patients-Mechanism of Action and Future Concepts.
Kamila Wojas-Krawczyk, Paweł Krawczyk, Michał Gil, Maciej Strzemski.
Cancers (Basel), 2021 Jul 03; 13(11). PMID: 34200219    Free PMC article.
Multidiscipline Immunotherapy-Based Rational Combinations for Robust and Durable Efficacy in Brain Metastases from Renal Cell Carcinoma.
Hye-Won Lee.
Int J Mol Sci, 2021 Jul 03; 22(12). PMID: 34208157    Free PMC article.
Comparing syngeneic and autochthonous models of breast cancer to identify tumor immune components that correlate with response to immunotherapy in breast cancer.
Jessica Castrillon Lal, Madeline G Townsend, +7 authors, Jennifer L Guerriero.
Breast Cancer Res, 2021 Aug 07; 23(1). PMID: 34353349    Free PMC article.
Serum sCD25 Protein as a Predictor of Lack of Long-Term Benefits from Immunotherapy in Non-Small Cell Lung Cancer: A Pilot Study.
Anna Siemiątkowska, Maciej Bryl, +4 authors, Franciszek K Główka.
Cancers (Basel), 2021 Aug 08; 13(15). PMID: 34359602    Free PMC article.
PD-1 Blockade for Hepatocellular Carcinoma: Current Research and Future Prospects.
Antonio D'Alessio, Lorenza Rimassa, Alessio Cortellini, David James Pinato.
J Hepatocell Carcinoma, 2021 Aug 14; 8. PMID: 34386437    Free PMC article.
Advances in immune therapies for the treatment of microsatellite instability‑high/deficient mismatch repair metastatic colorectal cancer (Review).
Khalil Choucair, Maluki Radford, +2 authors, Anwaar Saeed.
Int J Oncol, 2021 Aug 17; 59(3). PMID: 34396449    Free PMC article.
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.
Impact of Anti-PD-1 and Anti-CTLA-4 on the Human Immunodeficiency Virus (HIV) Reservoir in People Living With HIV With Cancer on Antiretroviral Therapy: The AIDS Malignancy Consortium 095 Study.
Thomas A Rasmussen, Lakshmi Rajdev, +16 authors, Sharon R Lewin.
Clin Infect Dis, 2021 Mar 08; 73(7). PMID: 33677480    Free PMC article.
First-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone (four cycles) in advanced non-small-cell lung cancer: CheckMate 9LA 2-year update.
M Reck, T-E Ciuleanu, +24 authors, T John.
ESMO Open, 2021 Oct 05; 6(5). PMID: 34607285    Free PMC article.
Epigenetic mechanisms of liver tumor resistance to immunotherapy.
Julie Sanceau, Angélique Gougelet.
World J Hepatol, 2021 Oct 12; 13(9). PMID: 34630870    Free PMC article.
Trial watch: intratumoral immunotherapy.
Juliette Humeau, Julie Le Naour, +2 authors, Jonathan G Pol.
Oncoimmunology, 2021 Oct 23; 10(1). PMID: 34676147    Free PMC article.
Molecular Analysis of Elements of Melanoma Insensitivity to TCR-Engineered Adoptive Cell Therapy.
Ali R Jazirehi.
Int J Mol Sci, 2021 Nov 14; 22(21). PMID: 34769156    Free PMC article.
Bridging Radiotherapy to Immunotherapy: The IFN-JAK-STAT Axis.
Lewis Zhichang Shi, James A Bonner.
Int J Mol Sci, 2021 Nov 28; 22(22). PMID: 34830176    Free PMC article.
Systematic Review.
From Bench to Bedside: How the Tumor Microenvironment Is Impacting the Future of Immunotherapy for Renal Cell Carcinoma.
Jonathan Anker, Justin Miller, +2 authors, Che-Kai Tsao.
Cells, 2021 Nov 28; 10(11). PMID: 34831452    Free PMC article.
Strategies to Improve the Antitumor Effect of Immunotherapy for Hepatocellular Carcinoma.
Rui Xing, Jinping Gao, Qi Cui, Qian Wang.
Front Immunol, 2021 Dec 14; 12. PMID: 34899747    Free PMC article.
The developing landscape of combinatorial therapies of immune checkpoint blockade with DNA damage repair inhibitors for the treatment of breast and ovarian cancers.
Lingling Zhu, Jiewei Liu, Jiang Chen, Qinghua Zhou.
J Hematol Oncol, 2021 Dec 22; 14(1). PMID: 34930377    Free PMC article.
Mechanisms of immune checkpoint inhibitor-mediated liver injury.
Layla Shojaie, Myra Ali, Andrea Iorga, Lily Dara.
Acta Pharm Sin B, 2022 Jan 14; 11(12). PMID: 35024302    Free PMC article.
Immune Reconstitution following High-Dose Chemotherapy and Autologous Stem Cell Transplantation with or without Pembrolizumab Maintenance Therapy in Patients with Lymphoma.
Reid W Merryman, Robert Redd, +23 authors, Jerome Ritz.
Transplant Cell Ther, 2021 Oct 21; 28(1). PMID: 34670169    Free PMC article.
First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in advanced non-small cell lung cancer: a subanalysis of Asian patients in CheckMate 9LA.
Thomas John, Hiroshi Sakai, +16 authors, Shun Lu.
Int J Clin Oncol, 2022 Feb 20; 27(4). PMID: 35182247    Free PMC article.
Immune Checkpoint Blockade in Lung Carcinoids with Aggressive Behaviour: One More Arrow in Our Quiver?
Sergio Di Molfetta, Tiziana Feola, +4 authors, Nike Group.
J Clin Med, 2022 Feb 26; 11(4). PMID: 35207291    Free PMC article.
Immune checkpoint blockade in HIV.
Celine Gubser, Chris Chiu, Sharon R Lewin, Thomas A Rasmussen.
EBioMedicine, 2022 Feb 06; 76. PMID: 35123267    Free PMC article.
First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients.
K J O'Byrne, K H Lee, +14 authors, J-S Lee.
ESMO Open, 2022 Feb 15; 7(1). PMID: 35158207    Free PMC article.
Association of Baseline and Pharmacodynamic Biomarkers With Outcomes in Patients Treated With the PD-1 Inhibitor Budigalimab.
Stacie L Lambert, Chun Zhang, +9 authors, Daniel Afar.
J Immunother, 2022 Jan 17; 45(3). PMID: 35034046    Free PMC article.
IFN-γ activates the tumor cell-intrinsic STING pathway through the induction of DNA damage and cytosolic dsDNA formation.
Hui Xiong, Yu Xi, +6 authors, Lequn Li.
Oncoimmunology, 2022 Mar 12; 11(1). PMID: 35273829    Free PMC article.
Addressing the Elephant in the Immunotherapy Room: Effector T-Cell Priming versus Depletion of Regulatory T-Cells by Anti-CTLA-4 Therapy.
Megan M Y Hong, Saman Maleki Vareki.
Cancers (Basel), 2022 Mar 26; 14(6). PMID: 35326731    Free PMC article.
Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer.
Kohei Shitara, Jaffer A Ajani, +26 authors, Yelena Y Janjigian.
Nature, 2022 Mar 25; 603(7903). PMID: 35322232    Free PMC article.