Parker Institute for Cancer Immunotherapy, San Francisco, California, USA.
Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Nat Med. 2017 May 5;23(5):540-547. doi: 10.1038/nm.4321.
The emergence of immuno-oncology as the first broadly successful strategy for metastatic cancer will require clinicians to integrate this new pillar of medicine with chemotherapy, radiation, and targeted small-molecule compounds. Of equal importance is gaining an understanding of the limitations and toxicities of immunotherapy. Immunotherapy was initially perceived to be a relatively less toxic approach to cancer treatment than other available therapies-and surely it is, when compared to those. However, as the use of immunotherapy becomes more common, especially as first- and second-line treatments, immunotoxicity and autoimmunity are emerging as the Achilles' heel of immunotherapy. In this Perspective, we discuss evidence that the occurrence of immunotoxicity bodes well for the patient, and describe mechanisms that might be related to the induction of autoimmunity. We then explore approaches to limit immunotoxicity, and discuss the future directions of research and reporting that are needed to diminish it.
免疫肿瘤学的出现是转移性癌症的首个广泛成功的策略，这将要求临床医生将这一新医学支柱与化疗、放疗和靶向小分子化合物相结合。同样重要的是，要了解免疫疗法的局限性和毒性。免疫疗法最初被认为是一种比其他可用疗法相对毒性较小的癌症治疗方法——与这些疗法相比，确实如此。然而，随着免疫疗法的应用越来越普遍，尤其是作为一线和二线治疗方法，免疫毒性和自身免疫性正在成为免疫疗法的阿喀琉斯之踵。在本观点中，我们讨论了免疫毒性发生对患者有利的证据，并描述了可能与自身免疫诱导相关的机制。然后，我们探讨了限制免疫毒性的方法，并讨论了减少免疫毒性所需的未来研究和报告方向。
