. 2018 Nov; 10(1):79.
doi: 10.1186/s13073-018-0588-4.

Recent advances in immunotherapies: from infection and autoimmunity, to cancer, and back again

Samantha L Bucktrout 1 Jeffrey A Bluestone 2 Fred Ramsdell 3 
  • PMID: 30376867
  •     99 References
  •     15 citations


For at least 300 years the immune system has been targeted to improve human health. Decades of work advancing immunotherapies against infection and autoimmunity paved the way for the current explosion in cancer immunotherapies. Pathways targeted for therapeutic intervention in autoimmune diseases can be modulated in the opposite sense in malignancy and infectious disease. We discuss the basic principles of the immune response, how these are co-opted in chronic infection and malignancy, and how these can be harnessed to treat disease. T cells are at the center of immunotherapy. We consider the complexity of T cell functional subsets, differentiation states, and extrinsic and intrinsic influences in the design, success, and lessons from immunotherapies. The integral role of checkpoints in the immune response is highlighted by the rapid advances in FDA approvals and the use of therapeutics that target the CTLA-4 and PD-1/PD-L1 pathways. We discuss the distinct and overlapping mechanisms of CTLA-4 and PD-1 and how these can be translated to combination immunotherapy treatments. Finally, we discuss how the successes and challenges in cancer immunotherapies, such as the collateral damage of immune-related adverse events following checkpoint inhibition, are informing treatment of autoimmunity, infection, and malignancy.

Protein kinase C-η controls CTLA-4-mediated regulatory T cell function.
Kok-Fai Kong, Guo Fu, +10 authors, Amnon Altman.
Nat Immunol, 2014 Apr 08; 15(5). PMID: 24705298    Free PMC article.
Highly Cited.
Cancer Immunotherapy Targets Based on Understanding the T Cell-Inflamed Versus Non-T Cell-Inflamed Tumor Microenvironment.
Thomas F Gajewski, Leticia Corrales, +3 authors, Stefani Spranger.
Adv Exp Med Biol, 2017 Dec 25; 1036. PMID: 29275462    Free PMC article.
Insulin-induced remission in new-onset NOD mice is maintained by the PD-1-PD-L1 pathway.
Brian T Fife, Indira Guleria, +7 authors, Jeffrey A Bluestone.
J Exp Med, 2006 Nov 23; 203(12). PMID: 17116737    Free PMC article.
Highly Cited.
Phase I/II study of ipilimumab for patients with metastatic melanoma.
Jeffrey S Weber, Steven O'Day, +5 authors, Evan Hersh.
J Clin Oncol, 2008 Nov 20; 26(36). PMID: 19018089
Highly Cited.
Nivolumab plus ipilimumab in advanced melanoma.
Jedd D Wolchok, Harriet Kluger, +21 authors, Mario Sznol.
N Engl J Med, 2013 Jun 04; 369(2). PMID: 23724867    Free PMC article.
Highly Cited.
Safety, correlative markers, and clinical results of adjuvant nivolumab in combination with vaccine in resected high-risk metastatic melanoma.
Geoffrey T Gibney, Ragini R Kudchadkar, +13 authors, Jeffrey S Weber.
Clin Cancer Res, 2014 Dec 20; 21(4). PMID: 25524312    Free PMC article.
Highly Cited.
Obstacles Posed by the Tumor Microenvironment to T cell Activity: A Case for Synergistic Therapies.
Kristin G Anderson, Ingunn M Stromnes, Philip D Greenberg.
Cancer Cell, 2017 Mar 16; 31(3). PMID: 28292435    Free PMC article.
Highly Cited. Review.
Ipilimumab Therapy in Patients With Advanced Melanoma and Preexisting Autoimmune Disorders.
Douglas B Johnson, Ryan J Sullivan, +18 authors, Joseph I Clark.
JAMA Oncol, 2015 Dec 04; 2(2). PMID: 26633184
Highly Cited.
Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death.
Y Ishida, Y Agata, K Shibahara, T Honjo.
EMBO J, 1992 Nov 01; 11(11). PMID: 1396582    Free PMC article.
Highly Cited.
Tumor immune profiling predicts response to anti-PD-1 therapy in human melanoma.
Adil I Daud, Kimberly Loo, +15 authors, Michael D Rosenblum.
J Clin Invest, 2016 Aug 16; 126(9). PMID: 27525433    Free PMC article.
Highly Cited.
Durability of complete responses in patients with metastatic cancer treated with high-dose interleukin-2: identification of the antigens mediating response.
S A Rosenberg, J C Yang, D E White, S M Steinberg.
Ann Surg, 1998 Sep 22; 228(3). PMID: 9742914    Free PMC article.
Highly Cited.
Programmed death ligand 1 regulates a critical checkpoint for autoimmune myocarditis and pneumonitis in MRL mice.
Julie A Lucas, Julia Menke, +3 authors, Vicki R Kelley.
J Immunol, 2008 Aug 08; 181(4). PMID: 18684942    Free PMC article.
Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal.
Brian T Fife, Kristen E Pauken, +6 authors, Jeffrey A Bluestone.
Nat Immunol, 2009 Sep 29; 10(11). PMID: 19783989    Free PMC article.
Highly Cited.
T cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition.
Enfu Hui, Jeanne Cheung, +8 authors, Ronald D Vale.
Science, 2017 Mar 11; 355(6332). PMID: 28280247    Free PMC article.
Highly Cited.
T-cell Responses to TP53 "Hotspot" Mutations and Unique Neoantigens Expressed by Human Ovarian Cancers.
Drew C Deniger, Anna Pasetto, +11 authors, Steven A Rosenberg.
Clin Cancer Res, 2018 Jun 02; 24(22). PMID: 29853601    Free PMC article.
Highly Cited.
Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: a randomized trial.
Joel M Kremer, Harry K Genant, +8 authors, Rene Westhovens.
Ann Intern Med, 2006 Jun 21; 144(12). PMID: 16785475
Highly Cited.
Safety Profile of Nivolumab Monotherapy: A Pooled Analysis of Patients With Advanced Melanoma.
Jeffrey S Weber, F Stephen Hodi, +9 authors, Caroline Robert.
J Clin Oncol, 2017 Jan 10; 35(7). PMID: 28068177
Highly Cited.
T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial.
Daniel W Lee, James N Kochenderfer, +16 authors, Crystal L Mackall.
Lancet, 2014 Oct 17; 385(9967). PMID: 25319501    Free PMC article.
Highly Cited.
PD-1 blockade induces responses by inhibiting adaptive immune resistance.
Paul C Tumeh, Christina L Harview, +23 authors, Antoni Ribas.
Nature, 2014 Nov 28; 515(7528). PMID: 25428505    Free PMC article.
Highly Cited.
Combining vaccines and immune checkpoint inhibitors to prime, expand, and facilitate effective tumor immunotherapy.
Julie M Collins, Jason M Redman, James L Gulley.
Expert Rev Vaccines, 2018 Jul 31; 17(8). PMID: 30058393    Free PMC article.
PD-1 inhibits antiviral immunity at the effector phase in the liver.
Yoshiko Iwai, Seigo Terawaki, +2 authors, Tasuku Honjo.
J Exp Med, 2003 Jul 09; 198(1). PMID: 12847136    Free PMC article.
Highly Cited.
Combination cancer immunotherapy and new immunomodulatory targets.
Kathleen M Mahoney, Paul D Rennert, Gordon J Freeman.
Nat Rev Drug Discov, 2015 Aug 01; 14(8). PMID: 26228759
Highly Cited. Review.
Genetic Mechanisms of Immune Evasion in Colorectal Cancer.
Catherine S Grasso, Marios Giannakis, +49 authors, Ulrike Peters.
Cancer Discov, 2018 Mar 08; 8(6). PMID: 29510987    Free PMC article.
Highly Cited.
Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4.
P Waterhouse, J M Penninger, +6 authors, T W Mak.
Science, 1995 Nov 10; 270(5238). PMID: 7481803
Highly Cited.
Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer.
Naiyer A Rizvi, Matthew D Hellmann, +21 authors, Timothy A Chan.
Science, 2015 Mar 15; 348(6230). PMID: 25765070    Free PMC article.
Highly Cited.
Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.
Suzanne L Topalian, F Stephen Hodi, +27 authors, Mario Sznol.
N Engl J Med, 2012 Jun 05; 366(26). PMID: 22658127    Free PMC article.
Highly Cited.
T-cell invigoration to tumour burden ratio associated with anti-PD-1 response.
Alexander C Huang, Michael A Postow, +31 authors, E John Wherry.
Nature, 2017 Apr 12; 545(7652). PMID: 28397821    Free PMC article.
Highly Cited.
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.
Management of immune-related adverse events and kinetics of response with ipilimumab.
Jeffrey S Weber, Katharina C Kähler, Axel Hauschild.
J Clin Oncol, 2012 May 23; 30(21). PMID: 22614989
Highly Cited. Review.
CAR T cell immunotherapy for human cancer.
Carl H June, Roddy S O'Connor, +2 authors, Michael C Milone.
Science, 2018 Mar 24; 359(6382). PMID: 29567707
Highly Cited. Review.
T cell metabolism drives immunity.
Michael D Buck, David O'Sullivan, Erika L Pearce.
J Exp Med, 2015 Aug 12; 212(9). PMID: 26261266    Free PMC article.
Highly Cited. Review.
Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia.
Jae H Park, Isabelle Rivière, +12 authors, Michel Sadelain.
N Engl J Med, 2018 Feb 01; 378(5). PMID: 29385376    Free PMC article.
Highly Cited.
TIGIT and PD-1 dual checkpoint blockade enhances antitumor immunity and survival in GBM.
Alice L Hung, Russell Maxwell, +20 authors, Michael Lim.
Oncoimmunology, 2018 Sep 18; 7(8). PMID: 30221069    Free PMC article.
Highly Cited.
Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial.
Howard L Kaufman, Jeffery Russell, +15 authors, Paul Nghiem.
Lancet Oncol, 2016 Sep 07; 17(10). PMID: 27592805    Free PMC article.
Highly Cited.
Coley's toxins in perspective.
C O Starnes.
Nature, 1992 May 07; 357(6373). PMID: 1574121
Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA4lg.
D J Lenschow, Y Zeng, +5 authors, J A Bluestone.
Science, 1992 Aug 07; 257(5071). PMID: 1323143
Highly Cited.
Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells.
John J O'Shea, William E Paul.
Science, 2010 Feb 27; 327(5969). PMID: 20185720    Free PMC article.
Highly Cited. Review.
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 future of immune checkpoint therapy.
Padmanee Sharma, James P Allison.
Science, 2015 Apr 04; 348(6230). PMID: 25838373
Highly Cited. Review.
Pooled Analysis of Long-Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma.
Dirk Schadendorf, F Stephen Hodi, +7 authors, Jedd D Wolchok.
J Clin Oncol, 2015 Feb 11; 33(17). PMID: 25667295    Free PMC article.
Highly Cited.
Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy.
Antoni Ribas, Reinhard Dummer, +17 authors, Georgina V Long.
Cell, 2017 Sep 09; 170(6). PMID: 28886381    Free PMC article.
Highly Cited.
Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice.
H Nishimura, T Okazaki, +8 authors, T Honjo.
Science, 2001 Feb 24; 291(5502). PMID: 11209085
Highly Cited.
Anti-CTLA-4 therapy broadens the melanoma-reactive CD8+ T cell response.
Pia Kvistborg, Daisy Philips, +13 authors, Ton N Schumacher.
Sci Transl Med, 2014 Sep 19; 6(254). PMID: 25232180
Highly Cited.
Distinct Cellular Mechanisms Underlie Anti-CTLA-4 and Anti-PD-1 Checkpoint Blockade.
Spencer C Wei, Jacob H Levine, +8 authors, James P Allison.
Cell, 2017 Aug 15; 170(6). PMID: 28803728    Free PMC article.
Highly Cited.
Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy.
Diego Chowell, Luc G T Morris, +17 authors, Timothy A Chan.
Science, 2017 Dec 09; 359(6375). PMID: 29217585    Free PMC article.
Highly Cited.
Selective targeting of engineered T cells using orthogonal IL-2 cytokine-receptor complexes.
Jonathan T Sockolosky, Eleonora Trotta, +15 authors, K Christopher Garcia.
Science, 2018 Mar 03; 359(6379). PMID: 29496879    Free PMC article.
Highly Cited.
Implications of the tumor immune microenvironment for staging and therapeutics.
Janis M Taube, Jérôme Galon, +8 authors, Ashley Cimino-Mathews.
Mod Pathol, 2017 Dec 02; 31(2). PMID: 29192647    Free PMC article.
Highly Cited. Review.
CTLA-4 control over Foxp3+ regulatory T cell function.
Kajsa Wing, Yasushi Onishi, +5 authors, Shimon Sakaguchi.
Science, 2008 Oct 11; 322(5899). PMID: 18845758
Highly Cited.
Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade.
Kristen E Pauken, Morgan A Sammons, +16 authors, E John Wherry.
Science, 2016 Oct 30; 354(6316). PMID: 27789795    Free PMC article.
Highly Cited.
Improved survival with ipilimumab in patients with metastatic melanoma.
F Stephen Hodi, Steven J O'Day, +26 authors, Walter J Urba.
N Engl J Med, 2010 Jun 08; 363(8). PMID: 20525992    Free PMC article.
Highly Cited.
Is autoimmunity the Achilles' heel of cancer immunotherapy?
Carl H June, Jeremy T Warshauer, Jeffrey A Bluestone.
Nat Med, 2017 May 06; 23(5). PMID: 28475571
Highly Cited.
Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4.
E A Tivol, F Borriello, +3 authors, A H Sharpe.
Immunity, 1995 Nov 01; 3(5). PMID: 7584144
Highly Cited.
Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma.
Omid Hamid, Caroline Robert, +23 authors, Antoni Ribas.
N Engl J Med, 2013 Jun 04; 369(2). PMID: 23724846    Free PMC article.
Highly Cited.
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.
Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor.
H Nishimura, M Nose, +2 authors, T Honjo.
Immunity, 1999 Sep 15; 11(2). PMID: 10485649
Highly Cited.
A clinical trial of CTLA-4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C.
Bruno Sangro, Carlos Gomez-Martin, +11 authors, Jesús Prieto.
J Hepatol, 2013 Mar 08; 59(1). PMID: 23466307
Highly Cited.
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.
Patterns of Clinical Response with Talimogene Laherparepvec (T-VEC) in Patients with Melanoma Treated in the OPTiM Phase III Clinical Trial.
Robert H I Andtbacka, Merrick Ross, +10 authors, Howard L Kaufman.
Ann Surg Oncol, 2016 Nov 03; 23(13). PMID: 27342831    Free PMC article.
Highly Cited.
PD-L2 is a second ligand for PD-1 and inhibits T cell activation.
Y Latchman, C R Wood, +18 authors, G J Freeman.
Nat Immunol, 2001 Feb 27; 2(3). PMID: 11224527
Highly Cited.
The epigenetic landscape of T cell exhaustion.
Debattama R Sen, James Kaminski, +16 authors, W Nicholas Haining.
Science, 2016 Oct 30; 354(6316). PMID: 27789799    Free PMC article.
Highly Cited.
Emerging principles in protease-based drug discovery.
Marcin Drag, Guy S Salvesen.
Nat Rev Drug Discov, 2010 Sep 03; 9(9). PMID: 20811381    Free PMC article.
Highly Cited. Review.
Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation.
G J Freeman, A J Long, +16 authors, T Honjo.
J Exp Med, 2000 Oct 04; 192(7). PMID: 11015443    Free PMC article.
Highly Cited.
Improved survival with T cell clonotype stability after anti-CTLA-4 treatment in cancer patients.
Edward Cha, Mark Klinger, +4 authors, Lawrence Fong.
Sci Transl Med, 2014 May 30; 6(238). PMID: 24871131    Free PMC article.
Highly Cited.
Expression of LAG-3 and efficacy of combination treatment with anti-LAG-3 and anti-PD-1 monoclonal antibodies in glioblastoma.
Sarah Harris-Bookman, Dimitrios Mathios, +18 authors, Michael Lim.
Int J Cancer, 2018 Sep 25; 143(12). PMID: 30248181    Free PMC article.
The initial phase of an immune response functions to activate regulatory T cells.
William E O'Gorman, Hans Dooms, +5 authors, Abul K Abbas.
J Immunol, 2009 Jun 23; 183(1). PMID: 19542444    Free PMC article.
The Immune Landscape of Cancer.
Vésteinn Thorsson, David L Gibbs, +55 authors, Ilya Shmulevich.
Immunity, 2018 Apr 10; 48(4). PMID: 29628290    Free PMC article.
Highly Cited.
CTLA-4 can function as a negative regulator of T cell activation.
T L Walunas, D J Lenschow, +5 authors, J A Bluestone.
Immunity, 1994 Aug 01; 1(5). PMID: 7882171
Highly Cited.
PD-1 identifies the patient-specific CD8⁺ tumor-reactive repertoire infiltrating human tumors.
Alena Gros, Paul F Robbins, +13 authors, Steven A Rosenberg.
J Clin Invest, 2014 Mar 29; 124(5). PMID: 24667641    Free PMC article.
Highly Cited.
Tumor Mutational Burden and Response Rate to PD-1 Inhibition.
Mark Yarchoan, Alexander Hopkins, Elizabeth M Jaffee.
N Engl J Med, 2017 Dec 21; 377(25). PMID: 29262275    Free PMC article.
Highly Cited.
Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial.
Achim Rittmeyer, Fabrice Barlesi, +23 authors, OAK Study Group.
Lancet, 2016 Dec 17; 389(10066). PMID: 27979383    Free PMC article.
Highly Cited.
Immune dysregulation in human subjects with heterozygous germline mutations in CTLA4.
Hye Sun Kuehn, Weiming Ouyang, +33 authors, Gulbu Uzel.
Science, 2014 Sep 13; 345(6204). PMID: 25213377    Free PMC article.
Highly Cited.
STAT3, STAT4, NFATc1, and CTCF regulate PD-1 through multiple novel regulatory regions in murine T cells.
James W Austin, Peiyuan Lu, +2 authors, Jeremy M Boss.
J Immunol, 2014 Apr 09; 192(10). PMID: 24711622    Free PMC article.
Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma.
Jeffrey S Weber, Ragini Reiney Kudchadkar, +11 authors, Y Ann Chen.
J Clin Oncol, 2013 Oct 23; 31(34). PMID: 24145345    Free PMC article.
Highly Cited.
Edward Jenner and the history of smallpox and vaccination.
Stefan Riedel.
Proc (Bayl Univ Med Cent), 2005 Oct 04; 18(1). PMID: 16200144    Free PMC article.
Nivolumab in Resected and Unresectable Metastatic Melanoma: Characteristics of Immune-Related Adverse Events and Association with Outcomes.
Morganna Freeman-Keller, Youngchul Kim, +3 authors, Jeffrey S Weber.
Clin Cancer Res, 2015 Oct 09; 22(4). PMID: 26446948    Free PMC article.
Highly Cited.
Genomic Features of Response to Combination Immunotherapy in Patients with Advanced Non-Small-Cell Lung Cancer.
Matthew D Hellmann, Tavi Nathanson, +29 authors, Jedd D Wolchok.
Cancer Cell, 2018 Apr 17; 33(5). PMID: 29657128    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.
Science, 2011 Apr 09; 332(6029). PMID: 21474713    Free PMC article.
Highly Cited.
Genomic correlates of response to CTLA-4 blockade in metastatic melanoma.
Eliezer M Van Allen, Diana Miao, +19 authors, Levi A Garraway.
Science, 2015 Sep 12; 350(6257). PMID: 26359337    Free PMC article.
Highly Cited.
Avidity and Bystander Suppressive Capacity of Human Regulatory T Cells Expressing De Novo Autoreactive T-Cell Receptors in Type 1 Diabetes.
Wen-I Yeh, Howard R Seay, +6 authors, Todd M Brusko.
Front Immunol, 2017 Nov 11; 8. PMID: 29123516    Free PMC article.
Targeting neoantigens to augment antitumour immunity.
Mark Yarchoan, Burles A Johnson, +2 authors, Elizabeth M Jaffee.
Nat Rev Cancer, 2017 Feb 25; 17(4). PMID: 28233802    Free PMC article.
Highly Cited. Review.
Chromatin states define tumour-specific T cell dysfunction and reprogramming.
Mary Philip, Lauren Fairchild, +11 authors, Andrea Schietinger.
Nature, 2017 May 18; 545(7655). PMID: 28514453    Free PMC article.
Highly Cited.
Molecular and cellular insights into T cell exhaustion.
E John Wherry, Makoto Kurachi.
Nat Rev Immunol, 2015 Jul 25; 15(8). PMID: 26205583    Free PMC article.
Highly Cited. Review.
A transcriptionally and functionally distinct PD-1+ CD8+ T cell pool with predictive potential in non-small-cell lung cancer treated with PD-1 blockade.
Daniela S Thommen, Viktor H Koelzer, +16 authors, Alfred Zippelius.
Nat Med, 2018 Jun 13; 24(7). PMID: 29892065    Free PMC article.
Highly Cited.
The immune contexture in human tumours: impact on clinical outcome.
Wolf Herman Fridman, Franck Pagès, Catherine Sautès-Fridman, Jérôme Galon.
Nat Rev Cancer, 2012 Mar 16; 12(4). PMID: 22419253
Highly Cited. Review.
TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells.
Sanjeev Mariathasan, Shannon J Turley, +39 authors, Thomas Powles.
Nature, 2018 Feb 15; 554(7693). PMID: 29443960    Free PMC article.
Highly Cited.
Increased reporting of fatal immune checkpoint inhibitor-associated myocarditis.
Javid J Moslehi, Joe-Elie Salem, +2 authors, Douglas B Johnson.
Lancet, 2018 Mar 15; 391(10124). PMID: 29536852    Free PMC article.
Highly Cited.
Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab.
A M Menzies, D B Johnson, +17 authors, G V Long.
Ann Oncol, 2016 Oct 01; 28(2). PMID: 27687304
Highly Cited.
First FDA Approval Agnostic of Cancer Site - When a Biomarker Defines the Indication.
Steven Lemery, Patricia Keegan, Richard Pazdur.
N Engl J Med, 2017 Oct 12; 377(15). PMID: 29020592
Highly Cited.
PD-1 Blockade in Tumors with Mismatch-Repair Deficiency.
Dung T Le, Jennifer N Uram, +32 authors, Luis A Diaz.
N Engl J Med, 2015 Jun 02; 372(26). PMID: 26028255    Free PMC article.
Highly Cited.
Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma.
Antoni Ribas, Richard Kefford, +21 authors, Axel Hauschild.
J Clin Oncol, 2013 Jan 09; 31(5). PMID: 23295794    Free PMC article.
Highly Cited.
Sipuleucel-T immunotherapy for castration-resistant prostate cancer.
Philip W Kantoff, Celestia S Higano, +11 authors, IMPACT Study Investigators.
N Engl J Med, 2010 Sep 08; 363(5). PMID: 20818862
Highly Cited.
Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease.
Christoph T Ellebrecht, Vijay G Bhoj, +9 authors, Aimee S Payne.
Science, 2016 Jul 02; 353(6295). PMID: 27365313    Free PMC article.
Highly Cited.
SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation.
Jens M Chemnitz, Richard V Parry, +2 authors, James L Riley.
J Immunol, 2004 Jul 09; 173(2). PMID: 15240681
Highly Cited.
Identification of a protein fragment of interleukin 2 responsible for vasopermeability.
Alan L Epstein, Myra M Mizokami, +2 authors, Leslie A Khawli.
J Natl Cancer Inst, 2003 May 22; 95(10). PMID: 12759392
The promise of low-dose interleukin-2 therapy for autoimmune and inflammatory diseases.
David Klatzmann, Abul K Abbas.
Nat Rev Immunol, 2015 Apr 18; 15(5). PMID: 25882245
Highly Cited. Review.
T-cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection.
Eoin F McKinney, James C Lee, +2 authors, Kenneth G C Smith.
Nature, 2015 Jul 01; 523(7562). PMID: 26123020    Free PMC article.
Highly Cited.
Long-term survival update for high-dose recombinant interleukin-2 in patients with renal cell carcinoma.
R I Fisher, S A Rosenberg, G Fyfe.
Cancer J Sci Am, 2000 Feb 24; 6 Suppl 1. PMID: 10685660
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.
Decisions about dendritic cells: past, present, and future.
Ralph M Steinman.
Annu Rev Immunol, 2011 Dec 06; 30. PMID: 22136168
Highly Cited. Review.
Mechanisms of immune-related adverse events during the treatment of cancer with immune checkpoint inhibitors.
Sophia C Weinmann, David S Pisetsky.
Rheumatology (Oxford), 2019 Dec 10; 58(Suppl 7). PMID: 31816080    Free PMC article.
TcellSubC: An Atlas of the Subcellular Proteome of Human T Cells.
Rubin Narayan Joshi, Charlotte Stadler, +4 authors, Mattias Vesterlund.
Front Immunol, 2019 Dec 19; 10. PMID: 31849937    Free PMC article.
Natural and Induced Tolerogenic Dendritic Cells.
Courtney A Iberg, Daniel Hawiger.
J Immunol, 2020 Feb 06; 204(4). PMID: 32015076    Free PMC article.
Immune Checkpoint Axes Are Dysregulated in Patients With Alcoholic Hepatitis.
Wei Li, Ying Xia, +8 authors, Qigui Yu.
Hepatol Commun, 2020 Apr 08; 4(4). PMID: 32258953    Free PMC article.
The Role of PD-1 in Acute and Chronic Infection.
Jil M Jubel, Zachary R Barbati, +2 authors, Frank A Schildberg.
Front Immunol, 2020 Apr 09; 11. PMID: 32265932    Free PMC article.
Imbalance of the CD226/TIGIT Immune Checkpoint Is Involved in the Pathogenesis of Primary Biliary Cholangitis.
Chuiwen Deng, Wenli Li, +5 authors, Yongzhe Li.
Front Immunol, 2020 Aug 15; 11. PMID: 32793241    Free PMC article.
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