Checkpoint blockade toxicity and immune homeostasis in the gastrointestinal tract

Frontiers in Immunology

Volumn 8, Issue NOV, 2017, Pages

  Dougan, Michael ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

Cancer immunotherapy; Checkpoint blockade; Gastrointestinal diseases; Immune related adverse events; Management

Indexed keywords

CHECKPOINT KINASE INHIBITOR; CORTICOSTEROID; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; INFLIXIMAB; IPILIMUMAB; PROGRAMMED DEATH 1 LIGAND 1; PROGRAMMED DEATH 1 RECEPTOR;

COLITIS; CYTOTOXIC T LYMPHOCYTE; CYTOTOXICITY; DIARRHEA; ENDOSCOPY; ENTERITIS; GASTROINTESTINAL MUCOSA; GASTROINTESTINAL TOXICITY; GASTROINTESTINAL TRACT; GENETIC ASSOCIATION; HEPATITIS; HOMEOSTASIS; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; MICROFLORA; PEPTOCLOSTRIDIUM DIFFICILE; PNEUMONIA; POLYMERASE CHAIN REACTION; REVIEW;

EID: 85034015225     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2017.01547     Document Type: Review

References (66)

1. Dougan M, Dranoff G. Immune therapy for cancer. Annu Rev Immunol (2009) 27:83-117. doi:10.1146/annurev.immunol.021908.132544
2. Baumeister SH, Freeman GJ, Dranoff G, Sharpe AH. Coinhibitory pathways in immunotherapy for cancer. Annu Rev Immunol (2016) 34:539-73. doi:10.1146/annurev-immunol-032414-112049
3. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med (2015) 373:23-34. doi:10.1056/NEJMoa1504030
4. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med (2010) 363:711-23. doi:10.1056/NEJMoa1003466
5. Robert C, Thomas L, Bondarenko I, O'Day S, Weber J, Garbe C, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med (2011) 364:2517-26. doi:10.1056/NEJMoa1104621
6. Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K, McDermott D, et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med (2015) 372:2006-17. doi:10.1056/NEJMoa1414428
7. Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med (2015) 372:320-30. doi:10.1056/NEJMoa1412082
8. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med (2015) 372:2509-20. doi:10.1056/NEJMoa1500596
9. Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med (2015) 372:2018-28. doi:10.1056/NEJMoa1501824
10. Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med (2015) 372:311-9. doi:10.1056/NEJMoa1411087
11. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer (2012) 12(4):252-64. doi:10.1038/nrc3239
12. Simpson TR, Li F, Montalvo-Ortiz W, Sepulveda MA, Bergerhoff K, Arce F, 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) 210:1695-710. doi:10.1038/ni.1774
13. Selby MJ, Engelhardt JJ, Quigley M, Henning KA, Chen T, Srinivasan M, et al. Anti-CTLA-4 antibodies of IgG2a isotype enhance antitumor activity through reduction of intratumoral regulatory T cells. Cancer Immunol Res (2013) 1:32-42. doi:10.1158/2326-6066.CIR-13-0013
14. Bulliard Y, Jolicoeur R, Windman M, Rue SM, Ettenberg S, Knee DA, et al. Activating Fc ? receptors contribute to the antitumor activities of immunoregulatory receptor-targeting antibodies. J Exp Med (2013) 210:1685-93. doi:10.4049/jimmunol.179.11.7365
15. Romano E, Kusio-Kobialka M, Foukas PG, Baumgaertner P, Meyer C, Ballabeni P, et al. Ipilimumab-dependent cell-mediated cytotoxicity of regulatory T cells ex vivo by nonclassical monocytes in melanoma patients. Proc Natl Acad Sci USA (2015) 112:6140-5. doi:10.1073/pnas.0712237105
16. Arlauckas SP, Garris CS, Kohler RH, Kitaoka M, Cuccarese MF, Yang KS, et al. In vivo imaging reveals a tumor-associated macrophage-mediated resistance pathway in anti-PD-1 therapy. Sci Transl Med (2017) 9(389):ii:eaal3604. doi:10.1126/scitranslmed.aal3604
17. Sharpe AH, Freeman GJ. The B7-CD28 superfamily. Nat Rev Immunol (2002) 2:116-26. doi:10.1038/35069118
18. Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, et al. Cancer immunology. mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science (2015) 348:124-8. doi:10.1126/science.aaa1348
19. Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science (2015) 348:69-74. doi:10.1126/science.aaa4971
20. Ott PA, Hu Z, Keskin DB, Shukla SA, Sun J, Bozym DJ, et al. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature (2017) 547:217-21. doi:10.1038/nature22991
21. Hodi FS, Chesney J, Pavlick AC, Robert C, Grossmann KF, McDermott DF, et al. 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. Lancet Oncol (2016) 17:1558-68. doi:10.1016/S1470-2045(16)30366-7
22. Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet (2017) 389:255-65. doi:10.1016/S0140-6736(16)32517-X
23. Peters S, Gettinger S, Johnson ML, Jänne PA, Garassino MC, Christoph D, et al. Phase II trial of atezolizumab as first-line or subsequent therapy for patients with programmed death-ligand 1-selected advanced non-small-cell lung cancer (BIRCH). J Clin Oncol (2017) 35(24):2781-9. doi:10.1200/JCO.2016.71.9476
24. Massard C, Gordon MS, Sharma S, Rafii S, Wainberg ZA, Luke J, et al. Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer. J Clin Oncol (2016) 34:3119-25. doi:10.1200/JCO.2016.67.9761
25. Larkin J, Lao CD, Urba WJ, McDermott DF, Horak C, Jiang J, et al. Efficacy and safety of nivolumab in patients with BRAFV600 mutant and BRAF wild-type advanced melanoma. JAMA Oncol (2015) 1:433. doi:10.1001/jamaoncol.2015.1184
26. Bellmunt J, de Wit R, Vaughn DJ, Fradet Y, Lee J-L, Fong L, et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med (2017) 376:1015-26. doi:10.1056/NEJMoa1613683
27. Schachter J, Ribas A, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006). Lancet (2017) 390(10105):1853-62. doi:10.1016/S0140-6736(17)31601-X
28. Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fülöp A, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med (2016) 375:1823-33. doi:10.1056/NEJMoa1606774
29. Eggermont AMM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, et al. Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy. N Engl J Med (2016) 375:1845-55. doi:10.1056/NEJMoa1611299
30. Wei SC, Levine JH, Cogdill AP, Zhao Y, Anang N-AAS, Andrews MC, et al. Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade. Cell (2017) 170:1120.e-33.e. doi:10.1016/j.cell.2017.07.024
31. Zaretsky JM, Garcia-Diaz A, Shin DS, Escuin-Ordinas H, Hugo W, Hu-Lieskovan S, et al. Mutations associated with acquired resistance to PD-1 blockade in melanoma. N Engl J Med (2016) 375:819-29. doi:10.1056/NEJMoa1604958
32. Hugo W, Zaretsky JM, Sun L, Song C, Moreno BH, Hu-Lieskovan S, et al. Genomic and transcriptomic features of response to anti-PD-1 therapy in metastatic melanoma. Cell (2016) 165:35-44. doi:10.1016/j.cell.2016.02.065
33. Rooney MS, Shukla SA, Wu CJ, Getz G, Hacohen N. Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell (2015) 160:48-61. doi:10.1016/j.cell.2014.12.033
34. Tivol EA, Borriello F, Schweitzer AN, Lynch WP, Bluestone JA, Sharpe AH. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity (1995) 3:541-7. doi:10.1016/1074-7613(95)90125-6
35. Sznol M, Ferrucci PF, Hogg D, Atkins MB, Wolter P, Guidoboni M, et al. Pooled analysis safety profile of nivolumab and ipilimumab combination therapy in patients with advanced melanoma. J Clin Oncol (2017). doi:10.1200/JCO.2016.72.1167
36. Kuehn HS, Ouyang W, Lo B, Deenick EK, Niemela JE, Avery DT, et al. Immune dysregulation in human subjects with heterozygous germline mutations in CTLA4. Science (2014) 345:1623-7. doi:10.1126/science.1255904
37. Zeissig S, Petersen B-S, Tomczak M, Melum E, Huc-Claustre E, Dougan SK, et al. Early-onset Crohn's disease and autoimmunity associated with a variant in CTLA-4. Gut (2015) 64:1889-97. doi:10.1136/gutjnl-2014-308541
38. Schubert D, Bode C, Kenefeck R, Hou TZ, Wing JB, Kennedy A, et al. Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations. Nat Med (2014) 20:1410-6. doi:10.1038/sj.leu.2403202
39. Nishimura H, Nose M, Hiai H, Minato N, Honjo T. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity (1999) 11:141-51. doi:10.1016/S1074-7613(00)80089-8
40. Latchman YE, Liang SC, Wu Y, Chernova T, Sobel RA, Klemm M, et al. PD-L1-deficient mice show that PD-L1 on T cells, antigen-presenting cells, and host tissues negatively regulates T cells. Proc Natl Acad Sci USA (2004) 101:10691-6. doi:10.1073/pnas.0307252101
41. van Elsas A, Hurwitz AA, Allison JP. Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation. J Exp Med (1999) 190:355-66
42. Curran MA, Montalvo W, Yagita H, Allison JP. 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 USA (2010) 107:4275-80. doi:10.4049/jimmunol.175.3.1586
43. Schadendorf D, Wolchok JD, Hodi FS, Chiarion-Sileni V, Gonzalez R, Rutkowski P, 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. J Clin Oncol (2017). doi:10.1200/JCO.2017.73.2289
44. Horvat TZ, Adel NG, Dang T-O, Momtaz P, Postow MA, Callahan MK, et al. Immune-related adverse events, need for systemic immunosuppression, and effects on survival and time to treatment failure in patients with melanoma treated with ipilimumab at memorial sloan kettering cancer center. J Clin Oncol (2015) 33:3193-8. doi:10.1200/JCO.2015.60.8448
45. Downey SG, Klapper JA, Smith FO, Yang JC, Sherry RM, Royal RE, et al. Prognostic factors related to clinical response in patients with metastatic melanoma treated by CTL-associated antigen-4 blockade. Clin Cancer Res (2007) 13:6681-8. doi:10.1158/1078-0432.CCR-07-0187
46. Beck KE, Blansfield JA, Tran KQ, Feldman AL, Hughes MS, Royal RE, et al. Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4. J Clin Oncol (2006) 24:2283-9. doi:10.1200/JCO.2005.04.5716
47. Arriola E, Wheater M, Karydis I, Thomas G, Ottensmeier C. Infliximab for IPILIMUMAB-related colitis-letter. Clin Cancer Res (2015) 21:5642-3. doi:10.1158/1078-0432.CCR-15-2471
48. Cutolo M. Autoimmune polyendocrine syndromes. Autoimmun Rev (2014) 13:85-9. doi:10.1016/j.autrev.2013.07.006
49. Cheng MH, Anderson MS. Monogenic autoimmunity. Annu Rev Immunol (2012) 30:393-427. doi:10.1146/annurev-immunol-020711-074953
50. Kurashima Y, Kiyono H. Mucosal ecological network of epithelium and immune cells for gut homeostasis and tissue healing. Annu Rev Immunol (2017) 35:119-47. doi:10.1146/annurev-immunol-051116-052424
51. Strober W, Fuss IJ, Blumberg RS. The immunology of mucosal models of inflammation. Annu Rev Immunol (2002) 20:495-549. doi:10.1146/annurev.immunol.20.100301.064816
52. Marthey L, Mateus C, Mussini C, Nachury M, Nancey S, Grange F, et al. Cancer immunotherapy with anti-CTLA-4 monoclonal antibodies induces an inflammatory bowel disease. J Crohns Colitis (2016) 10:395-401. doi:10.1093/ecco-jcc/jjv227
53. Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WEE, Poddubskaya E, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med (2015) 373:123-35. doi:10.1056/NEJMoa1504627
54. Gentile NM, D'Souza A, Fujii LL, Wu TT, Murray JA. Association between ipilimumab and celiac disease. Mayo Clin Proc (2013) 88:414-7. doi:10.1016/j.mayocp.2013.01.015
55. Abdel-Wahab N, Shah M, Suarez-Almazor ME. Adverse events associated with immune checkpoint blockade in patients with cancer: a systematic review of case reports. PLoS One (2016) 11:e0160221. doi:10.1371/journal.pone.0160221.s004
56. Kobayashi M, Yamaguchi O, Nagata K, Nonaka K, Ryozawa S. Acute hemorrhagic gastritis after nivolumab treatment. Gastrointes Endosc (2017) 86(5):915-6. doi:10.1016/j.gie.2017.04.033
57. Friedman CF, Proverbs-Singh TA, Postow MA. Treatment of the immune-related adverse effects of immune checkpoint inhibitors: a review. JAMA Oncol (2016) 2:1346-53. doi:10.1001/jamaoncol.2016.1051
58. Haanen JBAG, Carbonnel F, Robert C, Kerr KM, Peters S, Larkin J, et al. Management of toxicities from immunotherapy: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol (2017) 28:iv119-42. doi:10.1093/annonc/mdx225
59. Kim KW, Ramaiya NH, Krajewski KM, Shinagare AB, Howard SA, Jagannathan JP, et al. Ipilimumab-associated colitis: CT findings. AJR Am J Roentgenol (2013) 200:W468-74. doi:10.2214/AJR.12.9751
60. Chen Y, Sun J, Yang Y, Huang Y, Liu G. Malignancy risk of anti-tumor necrosis factor alpha blockers: an overview of systematic reviews and meta-analyses. Clin Rheumatol (2015) 35:1-18. doi:10.3109/09546634.2011.652064
61. Maneiro JR, Souto A, Gomez-Reino JJ. Risks of malignancies related to tofacitinib and biological drugs in rheumatoid arthritis: systematic review, meta-analysis, and network meta-analysis. Semin Arthritis Rheum (2017) 47(2):149-56. doi:10.1016/j.semarthrit.2017.02.007
62. Johnson DB, Sullivan RJ, Ott PA, Carlino MS, Khushalani NI, Ye F, et al. Ipilimumab therapy in patients with advanced melanoma and preexisting autoimmune disorders. JAMA Oncol (2016) 2(2):234-40. doi:10.1001/jamaoncol.2015.4368
63. Bergqvist V, Hertervig E, Gedeon P, Kopljar M, Griph H, Kinhult S, et al. Vedolizumab treatment for immune checkpoint inhibitor-induced enterocolitis. Cancer Immunol Immunother (2017) 66:581-92. doi:10.1007/s00262-017-1962-6
64. Feagan BG, Sandborn WJ, Gasink C, Jacobstein D, Lang Y, Friedman JR, et al. Ustekinumab as induction and maintenance therapy for Crohn's disease. N Engl J Med (2016) 375(20):1946-60. doi:10.1056/NEJMoa1602773
65. Sandborn WJ, Su C, Sands BE, D'Haens GR, Vermeire S, Schreiber S, et al. Tofacitinib as induction and maintenance therapy for ulcerative colitis. N Engl J Med (2017) 376(18):1723-36. doi:10.1056/NEJMoa1606910
66. Dubin K, Callahan MK, Ren B, Khanin R, Viale A, Ling L, et al. Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis. Nat Commun (2016) 7:10391. doi:10.1038/ncomms10391