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EDITORIAL

The pioneers behind immune checkpoint blockers awarded the Nobel Prize in physiology or medicine 2018

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Pages 1-8 | Received 16 Mar 2018, Accepted 29 Nov 2018, Published online: 30 Jan 2019

References

  • Antonia S, Mule JJ, Weber JS. Current developments of immunotherapy in the clinic. Curr Opin Immunol. 2004;16:130–136.
  • Klebanoff CA, Acquavella N, Yu Z, et al. Therapeutic cancer vaccines: are we there yet? Immunol Rev. 2011;239:27–44.
  • McGranahan N, Favero F, de Bruin EC, et al. Clonal status of actionable driver events and the timing of mutational processes in cancer evolution. Sci Transl Med. 2015;7:283ra254.
  • Awan FT, Byrd JC. New strategies in chronic lymphocytic leukemia: shifting treatment paradigms. Clin Cancer Res. 2014;20:5869–5874.
  • Baselga J, Coleman RE, Cortes J, et al. Advances in the management of HER2-positive early breast cancer. Crit Rev Oncol Hematol. 2017;119:113–122.
  • Grulich AE, van Leeuwen MT, Falster MO, et al. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet. 2007;370:59–67.
  • Yanik EL, Clarke CA, Snyder JJ, et al. Variation in cancer incidence among patients with ESRD during kidney function and nonfunction intervals. J Am Soc Nephrol. 2016;27:1495–1504.
  • Savill J, Dransfield I, Gregory C, et al. A blast from the past: clearance of apoptotic cells regulates immune responses. Nat Rev Immunol. 2002;2:965–975.
  • Green DR, Oguin TH, Martinez J. The clearance of dying cells: table for two. Cell Death Differ. 2016;23:915–926.
  • Goodall ML, Fitzwalter BE, Zahedi S, et al. The autophagy machinery controls cell death switching between apoptosis and necroptosis. Dev Cell. 2016;37:337–349.
  • Branca MA. Rekindling cancer vaccines. Nat Biotechnol. 2016;34:1019–1024.
  • Gubin MM, Zhang X, Schuster H, et al. Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature. 2014;515:577–581.
  • Heemskerk B, Kvistborg P, Schumacher TN. The cancer antigenome. EMBO J. 2013;32:194–203.
  • Alexandrov LB, Nik-Zainal S, Wedge DC, et al. Signatures of mutational processes in human cancer. Nature. 2013;500:415–421.
  • Rizvi NA, Hellmann MD, Snyder A, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348:124–128.
  • Yarchoan M, Hopkins A, Jaffee EM. Tumor mutational burden and response rate to PD-1 inhibition. N Engl J Med. 2017;377:2500–2501.
  • Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357:409–413.
  • Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science. 2015; 348:69–74.
  • Bonneville R, Krook MA, Miya J, et al. Landscape of microsatellite instability across 39 cancer types. Precis Oncol. 2017;0:1–15.
  • Stronen E, Toebes M, Kelderman S, et al. Targeting of cancer neoantigens with donor-derived T cell receptor repertoires. Science. 2016;352:1337–1341.
  • Galluzzi L, Buque A, Kepp O, et al. Immunogenic cell death in cancer and infectious disease. Nat Rev Immunol. 2017;17:97–111.
  • Tesniere A, Panaretakis T, Kepp O, et al. Molecular characteristics of immunogenic cancer cell death. Cell Death Differ. 2008;15:3–12.
  • Fuchs EJ, Matzinger P. Is cancer dangerous to the immune system? Semin Immunol. 1996;8:271–280.
  • Garg AD, Galluzzi L, Apetoh L, et al. Molecular and translational classifications of DAMPs in immunogenic cell death. Front Immunol. 2015;6:e588.
  • Pradeu T, Cooper EL. The danger theory: 20 years later. Front Immunol. 2012;3:287.
  • Eisenbacher JL, Schrezenmeier H, Jahrsdorfer B, et al. S100A4 and uric acid promote mesenchymal stromal cell induction of IL-10+/IDO + lymphocytes. J Immunol. 2014;192:6102–6110.
  • Sharabi AB, Lim M, DeWeese TL, et al. Radiation and checkpoint blockade immunotherapy: radiosensitisation and potential mechanisms of synergy. Lancet Oncol. 2015;16:e498–e509.
  • Lotfi R, Kaltenmeier C, Lotze MT, et al. Until death do us part: necrosis and oxidation promote the tumor microenvironment. Transfus Med Hemother. 2016;43:120–132.
  • Joyce JA, Fearon DT. T cell exclusion, immune privilege, and the tumor microenvironment. Science. 2015;348:74–80.
  • Ohta A. A metabolic immune checkpoint: adenosine in tumor microenvironment. Front Immunol. 2016;7:e109.
  • Vega VL, Rodriguez-Silva M, Frey T, et al. Hsp70 translocates into the plasma membrane after stress and is released into the extracellular environment in a membrane-associated form that activates macrophages. J Immunol. 2008;180:4299–4307.
  • Woo SR, Corrales L, Gajewski TF. Innate immune recognition of cancer. Annu Rev Immunol. 2015;33:445–474.
  • Esposito A, Criscitiello C, Curigliano G. Immune checkpoint inhibitors with radiotherapy and locoregional treatment: synergism and potential clinical implications. Curr Opin Oncol. 2015;27:445–451.
  • Wells AD, Malkovsky M. Heat shock proteins, tumor immunogenicity and antigen presentation: an integrated view. Immunol Today. 2000;21:129–132.
  • Horton R, Wilming L, Rand V, et al. Gene map of the extended human MHC. Nat Rev Genet. 2004;5:889–899.
  • Rock KL, Reits E, Neefjes J. Present yourself! By MHC class I and MHC class II molecules. Trends Immunol. 2016;37:724–737.
  • Sharma P, Allison JP. The future of immune checkpoint therapy. Science. 2015;348:56–61.
  • Harding FA, McArthur JG, Gross JA, et al. CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Nature. 1992;356:607–609.
  • Allison JP, Krummel MF. The Yin and Yang of T cell costimulation. Science. 1995;270:932–933.
  • Krummel MF, Allison JP. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J Exp Med. 1995;182:459–465.
  • McCoy KD, Le Gros G. The role of CTLA-4 in the regulation of T cell immune responses. Immunol Cell Biol. 1999;77:1–10.
  • Walunas TL, Lenschow DJ, Bakker CY, et al. CTLA-4 can function as a negative regulator of T cell activation. Immunity. 1994;1:405–413.
  • Curran MA, Montalvo W, Yagita H, et al. PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci U S A. 2010;107:4275–4280.
  • Simpson TR, Li F, Montalvo-Ortiz W, et al. Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. J Exp Med. 2013;210:1695–1710.
  • Dunn GP, Bruce AT, Ikeda H, et al. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002;3:991–998.
  • Dunn GP, Ikeda H, Bruce AT, et al. Interferon-gamma and cancer immunoediting. Immunol Res. 2005;32:231–245.
  • Ishida Y, Agata Y, Shibahara K, et al. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 1992;11:3887–3895.
  • Iwai Y, Ishida M, Tanaka Y, et al. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci U S A. 2002;99:12293–12297.
  • Freeman GJ, Long AJ, Iwai Y, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192:1027–1034.
  • Boussiotis VA. Molecular and biochemical aspects of the PD-1 checkpoint pathway. N Engl J Med. 2016;375:1767–1778.
  • Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252–264.
  • Sharma P, Allison JP. Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. Cell. 2015;161:205–214.
  • Topalian SL, Drake CG, Pardoll DM. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell. 2015;27:450–461.
  • Iwai Y, Hamanishi J, Chamoto K, et al. Cancer immunotherapies targeting the PD-1 signaling pathway. J Biomed Sci. 2017;24:26.
  • Wolchok JD, Neyns B, Linette G, et al. Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study. Lancet Oncol. 2010;11:155–164.
  • Callahan MK, Kluger H, Postow MA, et al. Nivolumab plus ipilimumab in patients with advanced melanoma: updated survival, response, and safety data in a phase I dose-escalation study. JCO. 2018;36:391–398.
  • Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2017;377:1345–1356.
  • Eggermont AM, Chiarion-Sileni V, Grob JJ, et al. Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy. N Engl J Med. 2016;375:1845–1855.
  • Eggermont AMM, Blank CU, Mandala M, et al. Adjuvant pembrolizumab versus placebo in resected stage III melanoma. N Engl J Med. 2018;378:1789–1801.
  • Weber J, Mandala M, Del Vecchio M, et al. Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med. 2017;377:1824–1835.
  • Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372:2018–2028.
  • Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373:1627–1639.
  • Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387:1540–1550.
  • Reck M, Rodriguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375:1823–1833.
  • Hellmann MD, Rizvi NA, Goldman JW, et al. Nivolumab plus ipilimumab as first-line treatment for advanced non-small-cell lung cancer (CheckMate 012): results of an open-label, phase 1, multicohort study. Lancet Oncol. 2017;18:31–41.
  • Chow LQM, Haddad R, Gupta S, et al. Antitumor activity of pembrolizumab in biomarker-unselected patients with recurrent and/or metastatic head and neck squamous cell carcinoma: results from the phase Ib KEYNOTE-012 expansion cohort. J Clin Oncol. 2016;34:3838–3845.
  • Ferris RL, Blumenschein G Jr, Fayette J, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375:1856–1867.
  • Kaufman HL, Russell J, Hamid O, et al. Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial. Lancet Oncol. 2016;17:1374–1385.
  • Nghiem PT, Bhatia S, Lipson EJ, et al. PD-1 blockade with pembrolizumab in advanced Merkel-Cell carcinoma. N Engl J Med. 2016;374:2542–2552.
  • Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373:1803–1813.
  • Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378:1277–1290.
  • Ross K, Jones RJ. Immune checkpoint inhibitors in renal cell carcinoma. Clin Sci. 2017;131:2627–2642.
  • Giridhar KV, Kohli M. Management of muscle-invasive urothelial cancer and the emerging role of immunotherapy in advanced urothelial cancer. Mayo Clin Proc. 2017;92:1564–1582.
  • Kamat AM, Bellmunt J, Galsky MD, et al. Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of bladder carcinoma. J Immunother Cancer. 2017;5:68.
  • Bellmunt J, de Wit R, Vaughn DJ, et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med. 2017;376:1015–1026.
  • Wang J, Reiss KA, Khatri R, et al. Immune therapy in GI malignancies: a review. J Clin Oncol. 2015;33:1745–1753.
  • Doi T, Piha-Paul SA, Jalal SI, et al. Safety and antitumor activity of the anti-programmed death-1 antibody pembrolizumab in patients with advanced esophageal carcinoma. Jco. 2018;36:61–67.
  • Overman MJ, McDermott R, Leach JL, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017;18:1182–1191.
  • Morris VK, Salem ME, Nimeiri H, et al. Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2017;18:446–453.
  • Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 2015;372:311–319.
  • Maly J, Alinari L. Pembrolizumab in classical Hodgkin's lymphoma. Eur J Haematol. 2016;97:219–227.
  • Villasboas JC, Ansell S. Checkpoint inhibition: programmed cell death 1 and programmed cell death 1 ligand inhibitors in Hodgkin lymphoma. Cancer J. 2016;22:17–22.
  • Lesokhin AM, Ansell SM, Armand P, et al. Nivolumab in patients with relapsed or refractory hematologic malignancy: preliminary results of a phase Ib study. J Clin Oncol. 2016;34:2698–2704.
  • Xu-Monette ZY, Zhou J, Young KH. PD-1 expression and clinical PD-1 blockade in B-cell lymphomas. Blood. 2018;131:68–83.
  • Chen PL, Roh W, Reuben A, et al. Analysis of immune signatures in longitudinal tumor samples yields insight into biomarkers of response and mechanisms of resistance to immune check point blockade. Cancer Discov. 2016;6:827–837.
  • Gibney GT, Weiner LM, Atkins MB. Predictive biomarkers for checkpoint inhibitor-based immunotherapy. Lancet Oncol. 2016;17:e542–e551.
  • Topalian SL, Taube JM, Anders RA, et al. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat Rev Cancer. 2016;16:275–287.
  • Chiou VL, Burotto M. Pseudoprogression and immune-related response in solid tumors. J Clin Oncol. 2015;33:3541–3543.
  • Hodi FS, Hwu WJ, Kefford R, et al. Evaluation of immune-related response criteria and RECIST v1.1 in patients with advanced melanoma treated with pembrolizumab. Jco. 2016;34:1510–1517.
  • Beer L, Hochmair M, Prosch H. Pitfalls in the radiological response assessment of immunotherapy. Memo. 2018;11:138–143.
  • Kim JM, Chen DS. Immune escape to PD-L1/PD-1 blockade: seven steps to success (or failure). Ann Oncol. 2016;27:1492–1504.
  • Patel SJ, Sanjana NE, Kishton RJ, et al. Identification of essential genes for cancer immunotherapy. Nature. 2017;548:537–542.
  • Sade-Feldman M, Jiao YJ, Chen JH, et al. Resistance to checkpoint blockade therapy through inactivation of antigen presentation. Nat Commun. 2017;8:1136.
  • Buque A, Bloy N, Aranda F, et al. Trial Watch: immunomodulatory monoclonal antibodies for oncological indications. Oncoimmunology. 2015;4:e1008814.
  • Hanahan D, Coussens LM. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell. 2012;21:309–322.
  • Anderson AC, Joller N, Kuchroo VK. Lag-3, Tim-3, and TIGIT: co-inhibitory receptors with specialized functions in immune regulation. Immunity. 2016;44:989–1004.
  • Cogdill AP, Andrews MC, Wargo JA. Hallmarks of response to immune checkpoint blockade. Br J Cancer. 2017;117:1–7.
  • Lines JL, Sempere LF, Broughton T, et al. VISTA is a novel broad-spectrum negative checkpoint regulator for cancer immunotherapy. Cancer Immunol Res. 2014;2:510–517.
  • Marin-Acevedo JA, Dholaria B, Soyano AE, et al. Next generation of immune checkpoint therapy in cancer: new developments and challenges. J Hematol Oncol. 2018;11:39.
  • Goldszmid RS, Dzutsev A, Viaud S, et al. Microbiota modulation of myeloid cells in cancer therapy. Cancer Immunol Res. 2015;3:103–109.
  • Iida N, Dzutsev A, Stewart CA, et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science. 2013;342:967–970.
  • Gopalakrishnan V, Helmink BA, Spencer CN, et al. The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy. Cancer Cell. 2018;33:570–580.
  • Gopalakrishnan V, Spencer CN, Nezi L, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359:97–103.
  • Matson V, Fessler J, Bao R, et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science. 2018;359:104–108.
  • Routy B, Le Chatelier E, Derosa L, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018;359:91–97.
  • Sivan A, Corrales L, Hubert N, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015;350:1084–1089.
  • Derosa L, Hellmann MD, Spaziano M, et al. Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer. Ann Oncol. 2018;29:1437–1444.
  • Champiat S, Dercle L, Ammari S, et al. Hyperprogressive disease is a new pattern of progression in cancer patients treated by anti-PD-1/PD-L1. Clin Cancer Res. 2017;23:1920–1928.
  • Saada-Bouzid E, Defaucheux C, Karabajakian A, et al. Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. Ann Oncol. 2017;28:1605–1611.
  • Sznol M, Ferrucci PF, Hogg D, et al. Pooled analysis safety profile of nivolumab and ipilimumab combination therapy in patients with advanced melanoma. Jco. 2017;35:3815–3822.
  • Kato S, Goodman A, Walavalkar V, et al. Hyperprogressors after immunotherapy: analysis of genomic alterations associated with accelerated growth rate. Clin Cancer Res. 2017;23:4242–4250.
  • Malkhasyan KA, Zakharia Y, Milhem M. Quality-of-life outcomes in patients with advanced melanoma: a review of the literature. Pigment Cell Melanoma Res. 2017;30:511–520.
  • Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology Clinical Practice guideline. Jco. 2018;36:1714–1768.
  • Hofmann L, Forschner A, Loquai C, et al. Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy. Eur J Cancer. 2016;60:190–209.
  • Michot JM, Bigenwald C, Champiat S, et al. Immune-related adverse events with immune checkpoint blockade: a comprehensive review. Eur J Cancer. 2016;54:139–148.
  • June CH, Warshauer JT, Bluestone JA. Is autoimmunity the Achilles' heel of cancer immunotherapy? Nat Med. 2017;23:540–547.
  • Schadendorf D, Wolchok JD, Hodi FS, et al. Efficacy and safety outcomes in patients with advanced melanoma who discontinued treatment with nivolumab and ipilimumab because of adverse events: a pooled analysis of randomized phase II and III trials. JCO. 2017;35:3807–3814.
  • Smyth MJ, Ngiow SF, Ribas A, et al. Combination cancer immunotherapies tailored to the tumour microenvironment. Nat Rev Clin Oncol. 2016;13:143–158.
  • Karachaliou N, Gonzalez-Cao M, Sosa A, et al. The combination of checkpoint immunotherapy and targeted therapy in cancer. Ann Transl Med. 2017;5:388.
  • Poon E, Mullins S, Watkins A, et al. The MEK inhibitor selumetinib complements CTLA-4 blockade by reprogramming the tumor immune microenvironment. J Immunother Cancer. 2017;5:63.
  • Zhang J, Bu X, Wang H, et al. Cyclin D-CDK4 kinase destabilizes PD-L1 via cullin 3-SPOP to control cancer immune surveillance. Nature. 2018;553:91–95.
  • Ariyan CE, Brady MS, Siegelbaum RH, et al. Robust antitumor responses result from local chemotherapy and CTLA-4 blockade. Cancer Immunol Res. 2018;6:189–200.
  • Govindan R, Szczesna A, Ahn MJ, et al. Phase III trial of ipilimumab combined with paclitaxel and carboplatin in advanced squamous non-small-cell lung cancer. J Clin Oncol. 2017;35:3449–3457.
  • Formenti SC, Demaria S. Combining radiotherapy and cancer immunotherapy: a paradigm shift. J Natl Cancer Inst. 2013;105:256–265.
  • Dahl O, Dale JE, Brydøy M. Rationale for combination of radiation therapy and immune checkpoint blockers to improve cancer treatment. Acta Oncol. 2019;58:xx.
  • Eggermont AM. Adjuvant ipilimumab in stage III melanoma: new landscape, new questions. Eur J Cancer. 2016;69:39–42.
  • Liu J, Blake SJ, Yong MC, et al. Improved efficacy of neoadjuvant compared to adjuvant immunotherapy to eradicate metastatic disease. Cancer Discov. 2016;6:1382–1399.
  • Forde PM, Chaft JE, Smith KN, et al. Neoadjuvant PD-1 blockade in resectable lung cancer. N Engl J Med. 2018;378:1976–1986.
  • Amaria RN, Reddy SM, Tawbi HA, et al. Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma. Nat Med. 2018;24:1649–1654.
  • Blank CU, Rozeman EA, Fanchi LF, et al. Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma. Nat Med. 2018;24:1655–1661.
  • Necchi A, Anichini A, Raggi D, et al. Pembrolizumab as neoadjuvant therapy before radical cystectomy in patients with muscle-invasive urothelial bladder carcinoma (PURE-01): an open-label, single-arm, phase II study. J Clin Oncol. 2018;JCO1801148.
  • Chalabi M, Fanchi LF, van den Berg J, et al. Neoadjuvant ipilimumab plus nivolumab in early stage colon cancer. ESMO Congress. 2018;2018. Abstract LBA 37.
  • Keung EZ, Ukponmwan EU, Cogdill AP, et al. The rationale and emerging use of neoadjuvant immune checkpoint blockade for solid malignancies. Ann Surg Oncol. 2018;25:1814–1827.
  • Winograd R, Byrne KT, Evans RA et al. Induction of T-cell immunity overcomes complete resistance to PD-1 and CTLA-4 blockade and improves survival in pancreatic carcinoma. Cancer Immunol Res. 2015;3:399–411.
  • Grasso CS, Giannakis M, Wells DK et al. Genetic Mechanisms of Immune Evasion in Colorectal Cancer. Cancer Discov. 2018;8:730–749.
  • Sharma P, Hu-Lieskovan S, Wargo JA, Ribas A. Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy. Cell 2017;168:707–723.
  • Gao J, Shi LZ, Zhao H et al. Loss of IFN-gamma Pathway Genes in Tumor Cells as a Mechanism of Resistance to Anti-CTLA-4 Therapy. Cell 2016;167:397–404. e399.
  • ] Shukla SA, Bachireddy P, Schilling B et al. Cancer-Germline Antigen Expression Discriminates Clinical Outcome to CTLA-4 Blockade. Cell 2018;173:624–633 .e628.
  • Andrews MC, Reuben A, Gopalakrishnan V, Wargo JA. Concepts Collide: Genomic, Immune, and Microbial Influences on the Tumor Microenvironment and Response to Cancer Therapy. Front Immunol. 2018;9:946.
  • Fearon DT. The carcinoma-associated fibroblast expressing fibroblast activation protein and escape from immune surveillance. Cancer Immunol Res. 2014;2:187–193.
  • Gordon SR, Maute RL, Dulken BW et al. PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature 2017;545:495–499.
  • Pitt JM, Vetizou M, Daillere R et al. Resistance Mechanisms to Immune-Checkpoint Blockade in Cancer: Tumor-Intrinsic and -Extrinsic Factors. Immunity 2016;44:1255–1269.
  • Koyama S, Akbay EA, Li YY et al. Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat Commun. 2016;7:10501.

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