Improved vaccine efficacy of tumor exosome compared to tumor lysate loaded dendritic cells in mice

Leukemia immunotherapy frequently does not meet expectation, one of the handicaps being tumor exosome (TEX)‐promoted immunosuppression. We here asked, using the mouse myeloid leukemia WEHI3B and the renal cell carcinoma line RENCA, whether dendritic cell (DC) vaccination suffices to counterregulate TEX‐induced immunosuppression and whether TEX could serve as tumor antigen for DC‐loading. DC‐vaccination significantly prolonged the survival time of WEHI3B‐bearing mice, TEX‐loaded DC (DC‐TEX) being superior to lysate‐loaded DC (DC‐lys), even an excess of TEX not interfering with immune response induction. The superior response to DC‐TEX was accompanied by an increase in WEHI3B‐specific CD4⁺ T cells, evaluated by trogocytosis and proliferation. Similar findings accounted for DC loaded with RENCA TEX. TEX was efficiently taken‐up by DC and TEX uptake supported CD11c, MHCII and IL12 upregulation in DC. Importantly, TEX was partly recruited into the MHCII‐loading compartment such that “TEX” presentation time and recovery in T cells significantly exceeded that of tumor‐lysate. Thus, TEX did not drive DC into a suppressive phenotype and were a superior antigen due to higher efficacy of TEX‐presentation that is supported by prolonged persistence, preferential processing in the MHCII‐loading compartment and pronounced trogocytosis by T helper cells. TEX is present in tumor patients' sera. TEX, recovered and enriched from patients' sera, might well provide an optimized, individual‐specific antigen source for DC‐loading and vaccination.