Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, NIHR Leeds Musculoskeletal Biomedical Research Unit, Chapel Allerton Hospital, Leeds, UK.
Department of Medicine 'B', Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Autoimmun Rev. 2020 Feb;19(2):102456. doi: 10.1016/j.autrev.2019.102456. Epub 2019 Dec 12.
Improved anti-tumour responses under immune checkpoint inhibition (ICI) are associated with concomitant autoimmune disease development termed immune related adverse events (irAEs), of which approximately 5% are rheumatic in nature. Generally, oncologists and other specialists vigorously treat irAEs in spite of the generally accepted beneficial effect of irAEs on tumour survival. Herein, we highlight mechanistic insights on how tumour responses and certain types of autoimmunity appear to be inextricably linked around CD8+ T-cell mediated responses and that strategies that interfere with such shared immunopathgenesis could impact of survival. We discuss the possible circumstances in which intensive immunosuppressive therapy for irAEs that occur with ICIs might blunt anti-tumour immunity. We also discuss potential therapeutic strategies for emergent ICI related autoimmunity and propose some treatment considerations and research questions to minimize the impact of overzealous immunosuppression strategies on tumour responses. Thus, refraining from using powerful therapeutic armamentarium to treat irAEs, especially when these are not considered as life-threating might improve the prognosis of ICI therapy.
免疫检查点抑制（ICI）下抗肿瘤反应的改善与同时发生的自身免疫性疾病发展有关，称为免疫相关不良事件（irAEs），其中约 5%为风湿性。通常，肿瘤学家和其他专家会积极治疗 irAEs，尽管 irAEs 对肿瘤生存的普遍有益影响已被普遍接受。在此，我们强调了关于肿瘤反应和某些类型的自身免疫如何似乎与 CD8+T 细胞介导的反应密切相关的机制见解，以及干扰这种共同免疫发病机制的策略可能会影响生存。我们讨论了在 ICI 中发生的 irAEs 进行强化免疫抑制治疗可能会削弱抗肿瘤免疫的可能情况。我们还讨论了新兴的 ICI 相关自身免疫的潜在治疗策略，并提出了一些治疗注意事项和研究问题，以最大程度地减少过度免疫抑制策略对肿瘤反应的影响。因此，避免使用强大的治疗武器来治疗 irAEs，尤其是当这些治疗不会危及生命时，可能会改善 ICI 治疗的预后。
