Cancer Immunotherapy and Uveitis: Balancing Anti-Tumor Immunity and Ocular Autoimmunity

• Type of Material: Article
• Authors: Steven Yeh, Emory University; Aditya Rali, Emory University; Ye Huang, University of Nebraska Medical Center, Omaha, NE
• Language: English
• Date: 2022-01-01
• Publisher: Emory University Libraries
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: PubMed Central
• Final Published Version (URL): http://dx.doi.org/10.1097/IIO.0000000000000434
• Title of Journal or Parent Work: International Ophthalmology Clinics
• Volume: 62
• Issue: 3
• Start Page: 49
• End Page: 63
• Grant/Funding Information: This project was supported by the National Eye Institute of the National Institutes of Health under award number R01 EY029594 (Yeh). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported by the Macula Society Retina Research Foundation, Association for Research in Vision and Ophthalmology Mallinckrodt Young Investigator Grant, and the Stanley M. Truhlsen Family Foundation.
• Keywords: Humans; targeted therapy; Neoplasms; Uveitis; immune-related adverse events; VKH-like syndrome, uveitis; Autoimmunity; checkpoint inhibitor; Immunotherapy
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Oncology

Abstract

Immune checkpoint inhibitors and targeted therapies are two classes of pharmacologic therapies used to treat metastatic malignancy by amplifying the immune system activity against cancerous cells. However, these drugs can consequently cause immune-related adverse events (irAEs). Albeit rare, cases of ocular IRAEs occurring among patients taking these drugs have been documented in literature, including a spectrum of uveitis findings. The classes of immune checkpoint inhibitors explored here include anti-CTLA4 (ipilimumab), anti-PD-1 (pembrolizumab, nivolumab) and anti-PDL-1 (atezolizumab, avelumab, durvalumab). Targeted therapies include the MEK inhibitors (trametinib) and BRAF enzyme inhibitors (dabrafenib, vemurafenib), both of which are involved in the MAPK/ERK signaling pathway responsible for cell proliferation. Reported cases of ocular irAEs caused by these drugs include anterior uveitis, posterior uveitis, panuveitis, and Vogt-Koyanagi-Harada (VKH)-like syndrome. Treatment can be determined on a case-by-case basis and depending on the severity of the irAE, may include temporary cessation of the offending drug, local corticosteroids, or systemic corticosteroids. Although the mechanism by which these ocular toxicities occur is not clearly elucidated, it is hypothesized that they are secondary to increased activity of auto-reactive T-cells. Further investigation into mechanisms underlying these inflammatory findings are relevant for cancer targeting, as well as insights into ocular autoimmune diseases.