Immune phenotype modulation in peripheral T and B cells after immune checkpoint inhibitor therapy in melanoma 2726

Abstract Description Immune checkpoint inhibitor (ICI) therapy has transformed cancer treatment by harnessing the immune system to combat tumors. However, the mechanisms underlying ICI-induced immune responses remain incompletely understood. Unveiling the immune landscape alterations induced by ICI therapy could facilitate the identification of novel biomarkers, as well as strategies to enhance therapeutic efficacy. In this study, we utilized single-cell RNA sequencing to analyze the transcriptomic and protein expression profiles of peripheral T and B cells in melanoma patients, comparing pre- and post-immune checkpoint inhibitor (ICI) treatment samples from those who developed immune-related adverse events. We identified and annotated a total of 6 CD4 T cell, 11 CD8 T cell, and 8 B cell clusters based on mRNA and protein profiling. Our findings indicate that ICI treatment decreases the proportion of a plasma B cell cluster and a stem cell memory CD8 T cell cluster, while increasing the proportion of regulatory T cells. Gene set enrichment analysis further revealed that ICI therapy significantly enhances TNF-α signaling via NF-κB across CD4, CD8 and B cell populations. Additionally, hypoxia and apoptosis pathways were notably elevated post-treatment in these immune cell populations. In summary, this study provides new insights into how ICI therapy modulates adaptive and humoral immune responses in melanoma patients, contributing to our understanding of ICI-induced immune dynamics. Funding Sources Supported by NIH/ NIA AG-083398; NIAID AI-158294 Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)