55P Mutations localized at the membrane predict immunotherapeutic efficacy in cancer treatment

In the clinic, immune checkpoint immunotherapy (ICI) is used to re-activate reactions against tumor neoantigens, leading striking remission in cancer patients’ tumors. However, complete or durable responses ICI treatment only occur a minority of patients. While level mutational burden (TMB) can be as predictive marker for responsiveness, we questioned whether subcellular localization neoantigens within cell additionally plays role. Using 3 human datasets with 1722 patients treated ICI, previously highlighted that bearing high proportion at membrane cells responded better anti-PD1. To decipher underlying immunological mechanisms, developed melanoma mouse model expresses membrane-bound soluble antigens and analyzed local systemic anti-tumor upon anti-PD1 immunotherapy. We engineered B16F10 express OVA intratumoral infiltration implantation C57BL6 mice. then compared growth wild-type mice depleted specific population. addition, via ex vivo antigen-specific restimulation splenocytes. demonstrated tumors have increased OVA, which rendered these highly susceptible rejection observed was dependent on antigen expressed cells, an rate dose low ones. surprisingly found independent immunoglobulin G (IgG), NK BatF3+ cross-presenting dendritic mostly relied CD8+ T cytotoxicity, partially CD4+ cells. this study, show important role immunogenicity subsequent responsiveness