A Guide to Cancer Immunotherapy: from T Cell Basic Science to Clinical Practice

Overview

Journal Nat Rev Immunol

Specialty Allergy & Immunology

Date 2020 May 21

PMID 32433532

Citations 1639

Authors

Alex D Waldman

Jill M Fritz

Michael J Lenardo

Affiliations

Soon will be listed here.

Abstract

The T lymphocyte, especially its capacity for antigen-directed cytotoxicity, has become a central focus for engaging the immune system in the fight against cancer. Basic science discoveries elucidating the molecular and cellular biology of the T cell have led to new strategies in this fight, including checkpoint blockade, adoptive cellular therapy and cancer vaccinology. This area of immunological research has been highly active for the past 50 years and is now enjoying unprecedented bench-to-bedside clinical success. Here, we provide a comprehensive historical and biological perspective regarding the advent and clinical implementation of cancer immunotherapeutics, with an emphasis on the fundamental importance of T lymphocyte regulation. We highlight clinical trials that demonstrate therapeutic efficacy and toxicities associated with each class of drug. Finally, we summarize emerging therapies and emphasize the yet to be elucidated questions and future promise within the field of cancer immunotherapy.

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References

Nishimura H, Okazaki T, Tanaka Y, Nakatani K, Hara M, Matsumori A . Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science. 2001; 291(5502):319-22. DOI: 10.1126/science.291.5502.319. View

Coyle A, Lehar S, Lloyd C, Tian J, Delaney T, Manning S . The CD28-related molecule ICOS is required for effective T cell-dependent immune responses. Immunity. 2000; 13(1):95-105. DOI: 10.1016/s1074-7613(00)00011-x. View

Nielsen M, Lund O, Buus S, Lundegaard C . MHC class II epitope predictive algorithms. Immunology. 2010; 130(3):319-28. PMC: 2913211. DOI: 10.1111/j.1365-2567.2010.03268.x. View

Kwon E, Hurwitz A, Foster B, Madias C, Feldhaus A, Greenberg N . Manipulation of T cell costimulatory and inhibitory signals for immunotherapy of prostate cancer. Proc Natl Acad Sci U S A. 1997; 94(15):8099-103. PMC: 21563. DOI: 10.1073/pnas.94.15.8099. View

Vignali D, Collison L, Workman C . How regulatory T cells work. Nat Rev Immunol. 2008; 8(7):523-32. PMC: 2665249. DOI: 10.1038/nri2343. View

Du X, Tang F, Liu M, Su J, Zhang Y, Wu W . A reappraisal of CTLA-4 checkpoint blockade in cancer immunotherapy. Cell Res. 2018; 28(4):416-432. PMC: 5939050. DOI: 10.1038/s41422-018-0011-0. View

Barber D, Wherry E, Masopust D, Zhu B, Allison J, Sharpe A . Restoring function in exhausted CD8 T cells during chronic viral infection. Nature. 2005; 439(7077):682-7. DOI: 10.1038/nature04444. View

Lee S, Moon J, Lee C, Kim H, Baek S, Hwang S . Abatacept alleviates severe autoimmune symptoms in a patient carrying a de novo variant in CTLA-4. J Allergy Clin Immunol. 2015; 137(1):327-330. DOI: 10.1016/j.jaci.2015.08.036. View

Ferris R, Blumenschein Jr G, Fayette J, Guigay J, Colevas A, Licitra L . Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med. 2016; 375(19):1856-1867. PMC: 5564292. DOI: 10.1056/NEJMoa1602252. View

10.

Berman D, Korman A, Peck R, Feltquate D, Lonberg N, Canetta R . The development of immunomodulatory monoclonal antibodies as a new therapeutic modality for cancer: the Bristol-Myers Squibb experience. Pharmacol Ther. 2014; 148:132-53. DOI: 10.1016/j.pharmthera.2014.11.017. View

11.

Rossy J, Williamson D, Gaus K . How does the kinase Lck phosphorylate the T cell receptor? Spatial organization as a regulatory mechanism. Front Immunol. 2012; 3:167. PMC: 3377954. DOI: 10.3389/fimmu.2012.00167. View

12.

Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky J, Desrichard A . Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med. 2014; 371(23):2189-2199. PMC: 4315319. DOI: 10.1056/NEJMoa1406498. View

13.

Chow M, Moller A, Smyth M . Inflammation and immune surveillance in cancer. Semin Cancer Biol. 2012; 22(1):23-32. DOI: 10.1016/j.semcancer.2011.12.004. View

14.

Gubin M, Zhang X, Schuster H, Caron E, Ward J, Noguchi T . Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature. 2014; 515(7528):577-81. PMC: 4279952. DOI: 10.1038/nature13988. View

15.

Sahin U, Tureci O . Personalized vaccines for cancer immunotherapy. Science. 2018; 359(6382):1355-1360. DOI: 10.1126/science.aar7112. View

16.

Antonia S, Villegas A, Daniel D, Vicente D, Murakami S, Hui R . Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017; 377(20):1919-1929. DOI: 10.1056/NEJMoa1709937. View

17.

Motzer R, Escudier B, Mcdermott D, George S, Hammers H, Srinivas S . Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015; 373(19):1803-13. PMC: 5719487. DOI: 10.1056/NEJMoa1510665. View

18.

Kowolik C, Topp M, Gonzalez S, Pfeiffer T, Olivares S, Gonzalez N . CD28 costimulation provided through a CD19-specific chimeric antigen receptor enhances in vivo persistence and antitumor efficacy of adoptively transferred T cells. Cancer Res. 2006; 66(22):10995-1004. DOI: 10.1158/0008-5472.CAN-06-0160. View

19.

Schmid P, Adams S, Rugo H, Schneeweiss A, Barrios C, Iwata H . Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2018; 379(22):2108-2121. DOI: 10.1056/NEJMoa1809615. View

20.

Nishimura H, Minato N, Nakano T, Honjo T . Immunological studies on PD-1 deficient mice: implication of PD-1 as a negative regulator for B cell responses. Int Immunol. 1998; 10(10):1563-72. DOI: 10.1093/intimm/10.10.1563. View