Institution: | 1. Department of Breast and Thyroid Surgery, The First Affiliated Hospital, Huzhou University School of Medicine, Huzhou, Zhejiang 313000, China;2. Department of Medical Oncology, Henan Provincial People’s Hospital, Zhengzhou, Henan 450003, China;3. Department of Chronic Disease Epidemiology, Yale School of Public Health, School of Medicine, Center for Biomedical Data Science, Yale Cancer Center, Yale University, 60 College Street, New Haven, CT 06520, USA;4. Department of General Surgery, The First Affiliated Hospital, Huzhou University School of Medicine, Huzhou, Zhejiang 313000, China;5. Department of Medicine and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA |
Abstract: | Cancer immunotherapy has brought a great revolution in the treatment of advanced human cancer. Immune checkpoint inhibitors (ICIs) that target cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death protein 1 pathway (PD-1/PD-L1) have been widely administrated in the past years and demonstrated promising in a variety of malignancies. While some patients show benefit from ICIs, others do not respond or even develop resistance to these therapies. Among the responders, the treatments are consequently accompanied with immune-related adverse effects (irAEs), which are diverse in their effected organs, degree of severity and timing. Some of the toxicities are fatal and result in discontinuance of immunotherapy. The toxicity profile from anti-CTLA-4 to anti-PD-1/PD-L1 immunotherapies is distinct from those caused by conventional anticancer therapies, though their presentation may be similar. In order to better help clinicians recognize, monitor and manage irAEs in a growing population of cancer patients who are receiving ICI therapy, this article summarizes the FDA approved ICIs and focuses on (1) existing toxic evidence related to ICIs, (2) occurrence of irAEs, (3) factors influencing tumor responders treated with ICIs, (4) predictive biomarkers of irAEs, and (5) new potential mechanisms of resistance to ICI therapy. |