Abstract
The immune tumor microenvironment is a dynamic ecosystem where B cells play critical roles in modulating immune checkpoint blockade (ICB) therapy responses. While traditionally seen as passive players in tumor immunity, recent evidence suggests that B cells actively influence antitumor responses. This study examines the role of B cells and their extracellular vesicles (EVs) in melanoma responses to ICB. Retrospective meta-analyses reveal increased B cell enrichment in ICB responders' pretreatment. Functional assays show that B cell depletion impairs T cell-mediated tumor cytotoxicity. EVs from melanoma tumors were analyzed, identifying miR-99a-5p in CD19+ EVs as up-regulated in responders. Silencing miR-99a-5p in B cells reduces T cell antitumor activity, suggesting its role in immune modulation. Mechanistically, miR-99a-5p promotes B cell maturation via class-switch recombination. These findings underscore B cells' impact on melanoma immunotherapy, offering insights into novel therapeutic strategies targeting B cell-related pathways.