Co‐immunization with L‐Myc enhances CD8⁺ or CD103⁺ DCs mediated tumor‐specific multi‐functional CD8⁺ T cell responses

Abstract

Abstract Renal carcinoma shows a high risk of invasion and metastasis without effective treatment. Herein, we developed a chitosan (CS) nanoparticle‐mediated DNA vaccine containing an activated factor L‐Myc and a tumor‐specific antigen CAIX for renal carcinoma treatment. The subcutaneous tumor models were intramuscularly immunized with CS‐pL‐Myc/pCAIX or control vaccine, respectively. Compared with single immunization group, the tumor growth was significantly suppressed in CS‐pL‐Myc/pCAIX co‐immunization group. The increased proportion and mature of CD11c + DCs, CD8 + CD11c + DCs and CD103 + CD11c + DCs were observed in the splenocytes from CS‐pL‐Myc/pCAIX co‐immunized mice. Furthermore, the enhanced antigen‐specific CD8 + T lymphocyte proliferation, cytotoxic T lymphocyte (CTL) responses, and multi‐functional CD8 + T cell induction were detected in CS‐pL‐Myc/pCAIX co‐immunization group compared with CS‐pCAIX immunization group. Of note, the depletion of CD8 T cells resulted in the reduction of CD8 + T cells or CD8 + CD11c + DCs and the loss of anti‐tumor efficacy induced by CS‐pL‐Myc/pCAIX vaccine, suggesting the therapeutic efficacy of the vaccine was required for CD8 + DCs and CD103 + DCs mediated CD8 + T cells responses. Likewise, CS‐pL‐Myc/pCAIX co‐immunization also significantly inhibited the lung metastasis of renal carcinoma models accompanied with the increased induction of multi‐functional CD8 + T cell responses. Therefore, these results indicated that CS‐pL‐Myc/pCAIX vaccine could effectively induce CD8 + DCs and CD103 + DCs mediated tumor‐specific multi‐functional CD8 + T cell responses and exert the anti‐tumor efficacy. This vaccine strategy offers a potential and promising approach for solid or metastatic tumor treatment.

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