Severe immune-related adverse events (irAEs) occur in up to 60% of patients with melanoma treated with immune checkpoint inhibitors (ICIs), and there’s no way to tell right now who’s likely to develop such toxicities prior to ICI treatment. In a study reported in Nature Medicine in January, a team co-led by Ludwig Stanford’s Aaron Newman analyzed 93 pre- and early on-ICI blood samples and three patient cohorts to identify characteristics predictive of adverse immune reactions. They found that a marked abundance of activated CD4 memory T cells and a high degree of sequence diversity in the genes encoding T cell receptors, which recognize antigens, are associated with severe irAEs. Aaron and his colleagues hypothesize that patients with this profile either have a tendency to develop autoimmune diseases or already have autoimmune reactions that aren’t clinically apparent. As an initial test of this idea, the researchers performed a similar analysis of blood samples from people diagnosed with autoimmune disorders like lupus and inflammatory bowel disease. They found in these cancer-free patients the same pattern of high CD4 memory T cells seen in melanoma patients with irAEs from immunotherapy. Their findings have implications for better clinical management of ICI therapy.
This article appeared in the May 2022 issue of Ludwig Link. Click here to download a copy (PDF, 2MB).