TMIC-42. LEVERAGING B CELL IMMUNITY TO PROMOTE IMMUNOTHERAPY IN GLIOBLASTOMA

Abstract Immunotherapy has revolutionized cancer treatment but yet to be translated into brain tumors. Studies in melanoma and sarcoma, amongst other models, have revealed the accumulation of germinal-center-like B cells as a key survival predictor post-PD1 blockade. We seek leverage cell immunity enhance immunotherapy effectiveness glioblastoma (GBM). In human GBM murine glioma we found that tumor microenvironment (TME) are activated, expression co-inhibitory molecules such CD32 CD72 blocks downstream effector function. Transcriptomic analysis showed high inhibitory TGFβ receptors on levels TGFβ1 cytokine TME. direct inhibition function through signaling could prevented with receptor Spatial multiplex immunofluorescence TME myeloid express also near cells, allowing for TGFβ-mediated inhibition. Blocking pathway via transgenic mice knockout or knockouts generation CT2A line knockdown, all demonstrated benefit more cells. There was increased T proliferation anti-tumor cytotoxicity. Finally, inhibiting αVβ8 integrin, required factor releases active TGFβ, is translatable approach animal survival. Dual αVβ8+PD1 blockade most potent well immunological memory against re-challenge. Analysis compartments after dual synergy, robust cellular functional differentiation plasmablasts Collectively, our study highlights importance remodeled boost effects GBM.