Allogeneic tumor cell-derived extracellular vesicles stimulate CD8 T cell response in colorectal cancer

Allogeneic tumor cell-derived extracellular vesicles stimulate CD8 T cell response in colorectal cancer

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Most colorectal cancer (CRC) patients present with a microsatellite-stable phenotype, rendering them resistant to immune checkpoint inhibitors (ICIs).Among the contributors to ICI resistance, tumor-derived extracellular vesicles (TEVs) have emerged as critical players.Previously we demonstrated that autologous transfer of TEVs without miR-424 can induce tumor antigen-specific immune responses in CRC models.Therefore, we postulated that allogeneic TEVs, modified to lack miR-424 and derived from an MC38 cells, could induce CD8+ T cell responses while restraining CT26 here cell-based tumor.Here, we show that prophylactic administration of MC38 TEVs, without miR-424, showed a significant augmentation in CD8+ T-cells within CT26 tumors.

This allogenic TEV effect was evident in CT26 tumors but not B16-F10 melanoma.Furthermore, we demonstrated the capacity of dendritic cells (DCs) to internalize TEVs, us polo assn mens sweaters a possible mechanism to elicit immune response.Our investigation of autologously administered DCs, which had been exposed to modified TEVs, underscores their potential to dampen tumor growth while elevating CD8+ T cell levels vis-a-vis MC38 wild-type TEVs exposed to DCs.Notably, the modified TEVs were well tolerated and did not increase peripheral blood cytokine levels.Our findings underscore the potential of modified allogeneic TEVs without immune-suppressive factors to elicit robust T cell responses and limit tumor growth.