Tissue resident memory B cells mediate local anti-cancer immunity 3448

Abstract Description Recent evidence demonstrates the existence of tissue resident memory B cells (BRM) in the lungs,where they provide long-lived protection against microbial infection,but it is unknown if analogous cells contribute to anti-cancer immunity.To dissect the dynamics and functional role of resident B cells in cancer progression,we used a cutaneous extracellular vesicle (EV) vaccination strategy to deliver DEL and OVA antigens locally.Adoptive transfer of antigen-specific B (Hy10,recognizing DEL) and T (OTII,recognizing OVA) cells allowed us to establish Hy10 BRM in specific localized regions of skin.Flow cytometric profiling revealed that these Hy10 BRM were enriched in expression of CD38,CD73,CXCR3, and CCR6 consistent with a phenotype associated with B cell memory and tissue residency.Challenging mice with MOC2 squamous cell carcinoma cells expressing OVA/DEL demonstrated that the presence of Hy10 BRM provided localized protection against tumor growth.Ongoing experiments aim to apply single cell RNA sequencing to transcriptionally profile human and murine tumor infiltrating BRM signatures.In addition,we are dissecting the mechanism through which BRM mediate anti-cancer immunity using both in vivo and in vitro models.Altogether,our results indicate that BRM can establish in skin and that such cells are primed for cancer immunosurveillance and killing.These findings expand our understanding of BRM protection role against cancer, and open new immunotherapies for targeting B cells. Funding Sources Melanoma Research Alliance, 1253470; Elsa U. Pardee Foundation; Knight Cancer Institute, OHSU Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)