3,658
Views
5
CrossRef citations to date
0
Altmetric
Clinical – Review

Biomarkers and risk factors for the early prediction of immune-related adverse events: a review

ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon, & ORCID Icon
Article: 2018894 | Received 10 Aug 2021, Accepted 11 Dec 2021, Published online: 02 Feb 2022

References

  • Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med. 2018;378:158–12. doi:10.1056/NEJMra1703481.
  • Sznol M, Ferrucci PF, Hogg D, Atkins MB, Wolter P, Guidoboni M, Lebbé C, Kirkwood JM, Schachter J, Daniels GA, et al. Pooled analysis safety profile of nivolumab and ipilimumab combination therapy in patients with advanced melanoma. J clin oncol. 2017;35(34):3815–22. doi:10.1200/JCO.2016.72.1167.
  • Eigentler TK, Hassel JC, Berking C, Aberle J, Bachmann O, Grünwald V, Kähler KC, Loquai C, Reinmuth N, Steins M, et al. Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy. Cancer Treat Rev. 2016;45:7–18. doi:10.1016/j.ctrv.2016.02.003.
  • Johnson DB, Balko JM, Compton ML, Chalkias S, Gorham J, Xu Y, Hicks M, Puzanov I, Alexander MR, Bloomer TL, et al. Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med. 2016;375(18):1749–55. doi:10.1056/NEJMoa1609214.
  • Berner F, Bomze D, Diem S, Ali OH, Fässler M, Ring S, Niederer R, Ackermann CJ, Baumgaertner P, Pikor N, et al. Association of checkpoint inhibitor-induced toxic effects with shared cancer and tissue antigens in non-small cell lung cancer. JAMA Oncol. 2019;5(7):1043–47. doi:10.1001/jamaoncol.2019.0402.
  • Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, Prieto PA, Vicente D, Hoffman K, Wei SC, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359(6371):97–103. doi:10.1126/science.aan4236.
  • Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y, Alegre ML, Luke JJ, Gajewski TF. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science. 2018;359(6371):104–08. doi:10.1126/science.aao3290.
  • Chaput N, Lepage P, Coutzac C, Soularue E, Le Roux K, Monot C, Boselli L, Routier E, Cassard L, Collins M, et al. Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab. Ann Oncol. 2017;28(6):1368–79. doi:10.1093/annonc/mdx108.
  • Das S, Johnson DB. Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors. J Immunother Cancer. 2019;7(1):306. doi:10.1186/s40425-019-0805-8.
  • Iwama S, De Remigis A, Callahan MK, Slovin SF, Wolchok JD, Caturegli P. Pituitary expression of CTLA-4 mediates hypophysitis secondary to administration of CTLA-4 blocking antibody. Sci Transl Med. 2014;6(230):230ra45. doi:10.1126/scitranslmed.3008002.
  • Jia XH, Geng LY, Jiang PP, Xu H, Nan KJ, Yao Y, Jiang -L-L, Sun H, Qin T-J, Guo H, et al. The biomarkers related to immune related adverse events caused by immune checkpoint inhibitors. J Exp Clin Cancer Res. 2020;39(1):284. doi:10.1186/s13046-020-01749-x.
  • El Osta B, Hu F, Sadek R, Chintalapally R, Tang SC. Not all immune-checkpoint inhibitors are created equal: meta-analysis and systematic review of immune-related adverse events in cancer trials. Crit Rev Oncol Hematol. 2017;119:1–12. doi:10.1016/j.critrevonc.2017.09.002.
  • Kottschade LA. Incidence and management of immune-related adverse events in patients undergoing treatment with immune checkpoint inhibitors. Curr Oncol Rep. 2018;20(3):24. doi:10.1007/s11912-018-0671-4.
  • Wang DY, Salem JE, Cohen JV, Chandra S, Menzer C, Ye F, Zhao S, Das S, Beckermann KE, Ha L, et al. Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA Oncol. 2018;4(12):1721–28. doi:10.1001/jamaoncol.2018.3923.
  • Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(1):23–34. doi:10.1056/NEJMoa1504030.
  • Suarez-Almazor ME, Kim ST, Abdel-Wahab N, Diab A. Review: immune-related adverse events with use of checkpoint inhibitors for immunotherapy of cancer. Arthritis Rheumatol. 2017;69:687–99. doi:10.1002/art.40043.
  • Barroso-Sousa R, Barry WT, Garrido-Castro AC, Hodi FS, Min L, Krop IE, Tolaney SM. Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens: a systematic review and meta-analysis. JAMA Oncol. 2018;4(2):173–82. doi:10.1001/jamaoncol.2017.3064.
  • Khunger M, Jain P, Rakshit S, Pasupuleti V, Hernandez AV, Stevenson J, Pennell NA, Velcheti V. Safety and efficacy of PD-1/PD-L1 inhibitors in treatment-naive and chemotherapy-refractory patients with non-small-cell lung cancer: a systematic review and meta-analysis. Clin Lung Cancer. 2018;19(3):e335–e48. doi:10.1016/j.cllc.2018.01.002.
  • Peeraphatdit TB, Wang J, Odenwald MA, Hu S, Hart J, Charlton MR. Hepatotoxicity from immune checkpoint inhibitors: a systematic review and management recommendation. Hepatology. 2020;72(1):315–29. doi:10.1002/hep.31227.
  • Haanen J, Carbonnel F, Robert C, Kerr KM, Peters S, Larkin J, Jordan K. Management of toxicities from immunotherapy: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29:iv264–iv6. doi:10.1093/annonc/mdy162.
  • Manohar S, Kompotiatis P, Thongprayoon C, Cheungpasitporn W, Herrmann J, Herrmann SM. Programmed cell death protein 1 inhibitor treatment is associated with acute kidney injury and hypocalcemia: meta-analysis. Nephrol Dial Transplant. 2019;34(1):108–17. doi:10.1093/ndt/gfy105.
  • Mahmood SS, Fradley MG, Cohen JV, Nohria A, Reynolds KL, Heinzerling LM, Sullivan RJ, Damrongwatanasuk R, Chen CL, Gupta D, et al. Myocarditis in patients treated with immune checkpoint inhibitors. J Am Coll Cardiol. 2018;71(16):1755–64. doi:10.1016/j.jacc.2018.02.037.
  • Hsu C, Marshall JL, He AR. Workup and management of immune-mediated hepatobiliary pancreatic toxicities that develop during immune checkpoint inhibitor treatment. The Oncologist. 2020;25(2):105–11. doi:10.1634/theoncologist.2018-0162.
  • Hasan Ali O, Berner F, Bomze D, Fässler M, Diem S, Cozzio A, Jörger M, Früh M, Driessen C, Lenz TL, et al. Human leukocyte antigen variation is associated with adverse events of checkpoint inhibitors. Eur J Cancer. 2019;107:8–14. doi:10.1016/j.ejca.2018.11.009.
  • Hasan Ali O, Bomze D, Ring SS, Berner F, Fässler M, Diem S, Abdou M-T, Hammers C, Emtenani S, Braun A, et al. BP180-specific IgG is associated with skin adverse events, therapy response, and overall survival in non-small cell lung cancer patients treated with checkpoint inhibitors. J Am Acad Dermatol. 2020;82(4):854–61. doi:10.1016/j.jaad.2019.08.045.
  • Fujisawa Y, Yoshino K, Otsuka A, Funakoshi T, Fujimura T, Yamamoto Y, Hata H, Gosho M, Tanaka R, Yamaguchi K, et al. Fluctuations in routine blood count might signal severe immune-related adverse events in melanoma patients treated with nivolumab. J Dermatol Sci. 2017;88(2):225–31. doi:10.1016/j.jdermsci.2017.07.007.
  • Shahabi V, Berman D, Chasalow SD, Wang L, Tsuchihashi Z, Hu B, Panting L, Jure-Kunkel M, Ji -R-R. Gene expression profiling of whole blood in ipilimumab-treated patients for identification of potential biomarkers of immune-related gastrointestinal adverse events. J Transl Med. 2013;11(1):75. doi:10.1186/1479-5876-11-75.
  • Isono T, Kagiyama N, Takano K, Hosoda C, Nishida T, Kawate E, Kobayashi Y, Ishiguro T, Takaku Y, Kurashima K, et al. Outcome and risk factor of immune-related adverse events and pneumonitis in patients with advanced or postoperative recurrent non-small cell lung cancer treated with immune checkpoint inhibitors. Thorac Cancer. 2021;12(2):153–64. doi:10.1111/1759-7714.13736.
  • Kurimoto C, Inaba H, Ariyasu H, Iwakura H, Ueda Y, Uraki S, Takeshima K, Furukawa Y, Morita S, Yamamoto Y, et al. Predictive and sensitive biomarkers for thyroid dysfunctions during treatment with immune-checkpoint inhibitors. Cancer Sci. 2020;111(5):1468–77. doi:10.1111/cas.14363.
  • Yano S, Ashida K, Sakamoto R, Sakaguchi C, Ogata M, Maruyama K, Sakamoto S, Ikeda M, Ohe K, Akasu S, et al. Human leucocyte antigen DR15, a possible predictive marker for immune checkpoint inhibitor-induced secondary adrenal insufficiency. Eur J Cancer. 2020;130:198–203. doi:10.1016/j.ejca.2020.02.049.
  • Stamatouli AM, Quandt Z, Perdigoto AL, Clark PL, Kluger H, Weiss SA, Gettinger S, Sznol M, Young A, Rushakoff R, et al. Collateral damage: insulin-dependent diabetes induced with checkpoint inhibitors. Diabetes. 2018;67(8):1471–80. doi:10.2337/dbi18-0002.
  • Cappelli LC, Dorak MT, Bettinotti MP, Bingham CO, Shah AA. Association of HLA-DRB1 shared epitope alleles and immune checkpoint inhibitor-induced inflammatory arthritis. Rheumatology. 2019;58(3):476–80. doi:10.1093/rheumatology/key358.
  • Puzanov I, Diab A, Abdallah K, Bingham CO 3rd, Brogdon C, Dadu R, Hamad L, Kim S, Lacouture ME, LeBoeuf NR, et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) toxicity management working group. J Immunother Cancer. 2017;5(1):95. doi:10.1186/s40425-017-0300-z.
  • Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, Chau I, Ernstoff MS, Gardner JM, Ginex P, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American society of clinical oncology clinical practice guideline. J clin oncol. 2018;36(17):1714–68. doi:10.1200/JCO.2017.77.6385.
  • Matsui Y, Makino T, Ishii N, Hashimoto T, Shimizu T. Detection of IgG antibodies to BP180 NC16a and C-terminal domains and LAD-1 in nivolumab-associated bullous pemphigoid. Eur J Dermatol. 2019;29(5):554–55. doi:10.1684/ejd.2019.3618.
  • Master SR, Robinson A, Mills GM, Mansour RP. Cardiovascular complications of immune checkpoint inhibitor therapy. J Clin Oncol. 2019;37(15_suppl):2568. doi:10.1200/JCO.2019.37.15_suppl.2568.
  • Salem JE, Manouchehri A, Moey M, Lebrun-Vignes B, Bastarache L, Pariente A, Gobert A, Spano J-P, Balko JM, Bonaca MP, et al. Cardiovascular toxicities associated with immune checkpoint inhibitors: an observational, retrospective, pharmacovigilance study. Lancet Oncol. 2018;19(12):1579–89. doi:10.1016/S1470-2045(18)30608-9.
  • Moslehi JJ, Salem JE, Sosman JA, Lebrun-Vignes B, Johnson DB. Increased reporting of fatal immune checkpoint inhibitor-associated myocarditis. Lancet. 2018;391(10124):933. doi:10.1016/S0140-6736(18)30533-6.
  • Okazaki T, Tanaka Y, Nishio R, Mitsuiye T, Mizoguchi A, Wang J, Ishida M, Hiai H, Matsumori A, Minato N, et al. Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice. Nat Med. 2003;9(12):1477–83. doi:10.1038/nm955.
  • Naidoo J, Wang X, Woo KM, Iyriboz T, Halpenny D, Cunningham J, Chaft JE, Segal NH, Callahan MK, Lesokhin AM, et al. Pneumonitis in patients treated with anti-programmed death-1/programmed death ligand 1 therapy. J clin oncol. 2017;35(7):709–17. doi:10.1200/JCO.2016.68.2005.
  • Gauci ML, Boudou P, Baroudjian B, Vidal-Trecan T, Da Meda L, Madelaine-Chambrin I, Basset-Seguin N, Bagot M, Pages C, Mourah S, et al. Occurrence of type 1 and type 2 diabetes in patients treated with immunotherapy (anti-PD-1 and/or anti-CTLA-4) for metastatic melanoma: a retrospective study. Cancer Immunol Immunother. 2018;67(8):1197–208. doi:10.1007/s00262-018-2178-0.
  • Iwama S, Kobayashi T, Arima H. Clinical characteristics, management, and potential biomarkers of endocrine dysfunction induced by immune checkpoint inhibitors. Endocrinol Metab. 2021;36(2):312–21. doi:10.3803/EnM.2021.1007.
  • Cunningham-Bussel A, Wang J, Prisco LC, Martin LW, Vanni KMM, Zaccardelli A, Nasrallah M, Gedmintas L, MacFarlane LA, Shadick NA, et al. Predictors of rheumatic immune-related adverse events and de novo inflammatory arthritis after immune checkpoint inhibitor treatment for cancer. Arthritis Rheumatol. 2021. doi:10.1002/art.41949.
  • Buder-Bakhaya K, Benesova K, Schulz C, Anwar H, Dimitrakopoulou-Strauss A, Weber TF, Enk A, Lorenz H-M, Hassel JC. Characterization of arthralgia induced by PD-1 antibody treatment in patients with metastasized cutaneous malignancies. Cancer Immunol Immunother. 2018;67(2):175–82. doi:10.1007/s00262-017-2069-9.
  • Liew DFL, Leung JLY, Liu B, Cebon J, Frauman AG, Buchanan RRC. Association of good oncological response to therapy with the development of rheumatic immune-related adverse events following PD-1 inhibitor therapy. Int J Rheum Dis. 2019;22(2):297–302. doi:10.1111/1756-185X.13444.
  • Liu Y, Jaquith JM, McCarthy-Fruin K, Zhu X, Zhou X, Li Y, Crowson C, Davis JM, Thanarajasingam U, Zeng H, et al. Immune checkpoint inhibitor-induced inflammatory arthritis: a novel clinical entity with striking similarities to seronegative rheumatoid arthritis. Clin Rheumatol. 2020;39(12):3631–37. doi:10.1007/s10067-020-05162-9.
  • Calabrese LH, Calabrese C, Cappelli LC. Rheumatic immune-related adverse events from cancer immunotherapy. Nat Rev Rheumatol. 2018;14(10):569–79. doi:10.1038/s41584-018-0074-9.
  • Huang YT, Chen YP, Lin WC, Su WC, Sun YT. Immune checkpoint inhibitor-induced myasthenia gravis. Front Neurol. 2020;11:634. doi:10.3389/fneur.2020.00634.
  • Haugh AM, Probasco JC, Johnson DB. Neurologic complications of immune checkpoint inhibitors. Expert Opin Drug Saf. 2020;19(4):479–88. doi:10.1080/14740338.2020.1738382.
  • Yshii LM, Gebauer CM, Pignolet B, Mauré E, Quériault C, Pierau M, Saito H, Suzuki N, Brunner-Weinzierl M, Bauer J, et al. CTLA4 blockade elicits paraneoplastic neurological disease in a mouse model. Brain. 2016;139(11):2923–34. doi:10.1093/brain/aww225.
  • Pavan A, Calvetti L, Dal Maso A, Attili I, Del Bianco P, Pasello G, Guarneri V, Aprile G, Conte P, Bonanno L, et al. Peripheral blood markers identify risk of immune-related toxicity in advanced non-small cell lung cancer treated with immune-checkpoint inhibitors. The Oncologist. 2019;24(8):1128–36. doi:10.1634/theoncologist.2018-0563.
  • Khoja L, Atenafu EG, Templeton A, Qye Y, Chappell MA, Saibil S, Hogg D, Butler MO, Joshua AM. The full blood count as a biomarker of outcome and toxicity in ipilimumab-treated cutaneous metastatic melanoma. Cancer Med. 2016;5(10):2792–99. doi:10.1002/cam4.878.
  • Abolhassani AR, Schuler G, Kirchberger MC, Heinzerling L. C-reactive protein as an early marker of immune-related adverse events. J Cancer Res Clin Oncol. 2019;145(10):2625–31. doi:10.1007/s00432-019-03002-1.
  • Fujimura T, Sato Y, Tanita K, Kambayashi Y, Otsuka A, Fujisawa Y, Yoshino K, Matsushita S, Funakoshi T, Hata H, et al. Serum levels of soluble CD163 and CXCL5 may be predictive markers for immune-related adverse events in patients with advanced melanoma treated with nivolumab: a pilot study. Oncotarget. 2018;9(21):15542–51. doi:10.18632/oncotarget.24509.
  • Das R, Bar N, Ferreira M, Newman AM, Zhang L, Bailur JK, Bacchiocchi A, Kluger H, Wei W, Halaban R, et al. Early B cell changes predict autoimmunity following combination immune checkpoint blockade. J Clin Invest. 2018;128(2):715–20. doi:10.1172/JCI96798.
  • Hirashima T, Kanai T, Suzuki H, Yoshida H, Matsusita A, Kawasumi H, Nasu S, Tanaka A, Morishita N, Kawahara K, et al. Significance of pre-treatment interferon-gamma release in patients with non-small-cell lung cancer receiving immune checkpoint inhibitors. Anticancer Res. 2020;40(12):6971–78. doi:10.21873/anticanres.14721.
  • Khan S, Khan SA, Luo X, Fattah FJ, Saltarski J, Gloria-mccutchen Y, Lu R, Xie Y, Li Q, Wakeland E, et al. Immune dysregulation in cancer patients developing immune-related adverse events. Br J Cancer. 2019;120(1):63–68. doi:10.1038/s41416-018-0155-1.
  • Jing Y, Liu J, Ye Y, Pan L, Deng H, Wang Y, Yang Y, Diao L, Lin SH, Mills GB, et al. Multi-omics prediction of immune-related adverse events during checkpoint immunotherapy. Nat Commun. 2020;11(1):4946. doi:10.1038/s41467-020-18742-9.
  • Sugisaka J, Toi Y, Taguri M, Kawashima Y, Aiba T, Kawana S, Saito R, Aso M, Tsurumi K, Suzuki K, et al. Relationship between programmed cell death protein ligand 1 expression and immune-related adverse events in non-small-cell lung cancer patients treated with pembrolizumab. Jma J. 2020;3(1):58–66. doi:10.31662/jmaj.2019-0005.
  • Van Gorp H, Delputte PL, Nauwynck HJ. Scavenger receptor CD163, a Jack-of-all-trades and potential target for cell-directed therapy. Mol Immunol. 2010;47(7–8):1650–60. doi:10.1016/j.molimm.2010.02.008.
  • Fujimura T, Kakizaki A, Furudate S, Aiba S. A possible interaction between periostin and CD163+ skin-resident macrophages in pemphigus vulgaris and bullous pemphigoid. Exp Dermatol. 2017;26(12):1193–98. doi:10.1111/exd.13157.
  • Sakai S, Kauffman KD, Sallin MA, Sharpe AH, Young HA, Ganusov VV, Barber DL. CD4 T cell-derived IFN-γ plays a minimal role in control of pulmonary mycobacterium tuberculosis infection and must be actively repressed by PD-1 to prevent lethal disease. PLoS Pathog. 2016;12(5):e1005667. doi:10.1371/journal.ppat.1005667.
  • Takada S, Hirokazu H, Yamagishi K, Hideki S, Masayuki E. Predictors of the onset of type 1 diabetes obtained from real-world data analysis in cancer patients treated with immune checkpoint inhibitors. Asian Pac J Cancer Prev. 2020;21:1697–99. doi:10.31557/APJCP.2020.21.6.1697.
  • Duma N, Abdel-Ghani A, Yadav S, Hoversten KP, Reed CT, Sitek AN, Enninga EAL, Paludo J, Aguilera JV, Leventakos K, et al. Sex differences in tolerability to anti-programmed cell death protein 1 therapy in patients with metastatic melanoma and non-small cell lung cancer: are we all equal? Oncologist. 2019;24(11):e1148–e55. doi:10.1634/theoncologist.2019-0094.
  • Kartolo A, Sattar J, Sahai V, Baetz T, Lakoff JM. Predictors of immunotherapy-induced immune-related adverse events. Curr Oncol. 2018;25(5):e403–e10. doi:10.3747/co.25.4047.
  • Nosaki K, Saka H, Hosomi Y, Baas P, de Castro G Jr., Reck M, Wu Y-L, Brahmer JR, Felip E, Sawada T, et al. Safety and efficacy of pembrolizumab monotherapy in elderly patients with PD-L1-positive advanced non-small-cell lung cancer: pooled analysis from the KEYNOTE-010, KEYNOTE-024, and KEYNOTE-042 studies. Lung Cancer. 2019;135:188–95. doi:10.1016/j.lungcan.2019.07.004.
  • Marur S, Singh H, Mishra-Kalyani P, Larkins E, Keegan P, Sridhara R, Blumenthal GM, Pazdur R. FDA analyses of survival in older adults with metastatic non-small cell lung cancer in controlled trials of PD-1/PD-L1 blocking antibodies. Semin Oncol. 2018;45:220–25. doi:10.1053/j.seminoncol.2018.08.007.
  • Okada N, Matsuoka R, Sakurada T, Goda M, Chuma M, Yagi K, Zamami Y, Nishioka Y, Ishizawa K. Risk factors of immune checkpoint inhibitor-related interstitial lung disease in patients with lung cancer: a single-institution retrospective study. Sci Rep. 2020;10(1):13773. doi:10.1038/s41598-020-70743-2.
  • Nakanishi Y, Masuda T, Yamaguchi K, Sakamoto S, Horimasu Y, Nakashima T, Miyamoto S, Tsutani Y, Iwamoto H, Fujitaka K, et al. Pre-existing interstitial lung abnormalities are risk factors for immune checkpoint inhibitor-induced interstitial lung disease in non-small cell lung cancer. Respir Investig. 2019;57(5):451–59. doi:10.1016/j.resinv.2019.05.002.
  • Kanai O, Kim YH, Demura Y, Kanai M, Ito T, Fujita K, Yoshida H, Akai M, Mio T, Hirai T. Efficacy and safety of nivolumab in non-small cell lung cancer with preexisting interstitial lung disease. Thorac Cancer. 2018;9(7):847–55 doi:10.1111/1759-7714.12759.
  • Cui P, Liu Z, Wang G, Ma J, Qian Y, Zhang F, Han C, Long Y, Li Y, Zheng X, et al. Risk factors for pneumonitis in patients treated with anti-programmed death-1 therapy: a case-control study. Cancer Med. 2018;7(8):4115–20. doi:10.1002/cam4.1579.
  • Cortellini A, Bersanelli M, Santini D, Buti S, Tiseo M, Cannita K, Perrone F, Giusti R, De Tursi M, Zoratto F, et al. Another side of the association between body mass index (BMI) and clinical outcomes of cancer patients receiving programmed cell death protein-1 (PD-1)/ Programmed cell death-ligand 1 (PD-L1) checkpoint inhibitors: a multicentre analysis of immune-related adverse events. Eur J Cancer. 2020;128:17–26. doi:10.1016/j.ejca.2019.12.031.
  • Wang S, Cowley LA, Liu XS. Sex differences in cancer immunotherapy efficacy, biomarkers, and therapeutic strategy. Molecules. 2019;24(18):3214. doi:10.3390/molecules24183214.
  • Weber JS, Hodi FS, Wolchok JD, Topalian SL, Schadendorf D, Larkin J, Sznol M, Long GV, Li H, Waxman IM, et al. Safety profile of nivolumab monotherapy: a pooled analysis of patients with advanced melanoma. J clin oncol. 2017;35(7):785–92. doi:10.1200/JCO.2015.66.1389.
  • Hofmann L, Forschner A, Loquai C, Goldinger SM, Zimmer L, Ugurel S, Schmidgen MI, Gutzmer R, Utikal JS, Göppner D, et al. Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy. Eur J Cancer. 2016;60:190–209. doi:10.1016/j.ejca.2016.02.025.
  • Sugano T, Seike M, Saito Y, Kashiwada T, Terasaki Y, Takano N, Hisakane K, Takahashi S, Tanaka T, Takeuchi S, et al. Immune checkpoint inhibitor-associated interstitial lung diseases correlate with better prognosis in patients with advanced non-small-cell lung cancer. Thorac Cancer. 2020;11(4):1052–60. doi:10.1111/1759-7714.13364.
  • Daud AI, Wolchok JD, Robert C, Hwu WJ, Weber JS, Ribas A, Hodi FS, Joshua AM, Kefford R, Hersey P, et al. Programmed death-ligand 1 expression and response to the anti-programmed death 1 antibody pembrolizumab in melanoma. J clin oncol. 2016;34(34):4102–09. doi:10.1200/JCO.2016.67.2477.
  • Goodman AM, Kato S, Bazhenova L, Patel SP, Frampton GM, Miller V, Stephens PJ, Daniels GA, Kurzrock R. Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers. Mol Cancer Ther. 2017;16(11):2598–608 doi:10.1158/1535-7163.MCT-17-0386.
  • Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509–20. doi:10.1056/NEJMoa1500596.
  • Adam T, Becker TM, Chua W, Bray V, Roberts TL. The multiple potential biomarkers for predicting immunotherapy response-finding the needle in the haystack. Cancers (Basel). 2021;13(2):277. doi:10.3390/cancers13020277.
  • Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357(6349):409–13. doi:10.1126/science.aan6733.
  • Eshghi N, Garland LL, Nia E, Betancourt R, Krupinski E, Kuo PH. (18)F-FDG PET/CT can predict development of thyroiditis due to immunotherapy for lung cancer. J Nucl Med Technol. 2018;46:260–64. doi:10.2967/jnmt.117.204933.
  • Colen RR, Fujii T, Bilen MA, Kotrotsou A, Abrol S, Hess KR, Hajjar J, Suarez-Almazor ME, Alshawa A, Hong DS, et al. Radiomics to predict immunotherapy-induced pneumonitis: proof of concept. Invest New Drugs. 2018;36(4):601–07. doi:10.1007/s10637-017-0524-2.
  • June CH, Warshauer JT, Bluestone JA. Is autoimmunity the Achilles‘ heel of cancer immunotherapy? Nat Med. 2017;23(5):540–47. doi:10.1038/nm.4321.
  • Von Itzstein MS, Khan S, Gerber DE. Investigational biomarkers for checkpoint inhibitor immune-related adverse event prediction and diagnosis. Clin Chem. 2020;66(6):779–93. doi:10.1093/clinchem/hvaa081.
  • Akinci Ozyurek B, Sahin Ozdemirel T, Buyukyaylaci Ozden S, Erdogan Y, Kaplan B, Kaplan T. Prognostic value of the Neutrophil to Lymphocyte Ratio (NLR) in lung cancer cases. Asian Pac J Cancer Prev. 2017;18(5):1417–21. doi:10.22034/APJCP.2017.18.5.1417.
  • Nakaya A, Kurata T, Yoshioka H, Takeyasu Y, Niki M, Kibata K, Satsutani N, Ogata M, Miyara T, Nomura S, et al. Neutrophil-to-lymphocyte ratio as an early marker of outcomes in patients with advanced non-small-cell lung cancer treated with nivolumab. Int J Clin Oncol. 2018;23(4):634–40. doi:10.1007/s10147-018-1250-2.
  • Gu X, Sun S, Gao XS, Xiong W, Qin S, Qi X, Ma M, Li X, Zhou D, Wang W, et al. Prognostic value of platelet to lymphocyte ratio in non-small cell lung cancer: evidence from 3,430 patients. Sci Rep. 2016;6(1):23893. doi:10.1038/srep23893.
  • Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, Molina J, Kim J-H, Arvis CD, Ahn M-J, 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(10027):1540–50. doi:10.1016/S0140-6736(15)01281-7.
  • Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375(19):1823–33. doi:10.1056/NEJMoa1606774.
  • Mok TSK, Wu YL, Kudaba I, Kowalski DM, Cho BC, Turna HZ, Castro G, Srimuninnimit V, Laktionov KK, Bondarenko I, et al. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019;393(10183):1819–30. doi:10.1016/S0140-6736(18)32409-7.
  • Kanarek N, Petrova B, Sabatini DM. Dietary modifications for enhanced cancer therapy. Nature. 2020;579(7800):507–17. doi:10.1038/s41586-020-2124-0.
  • Fillon M. Exercise and nutrition may prolong the lives of patients with colon cancer. CA Cancer J Clin. 2018;68(5):319–21. doi:10.3322/caac.21430.