Abstract

Introduction: Resident memory CD8+ T (Trm) cells stably reside in non-lymphoid tissues and mediate potent protective immunity. Upon antigen recognition, Trm cells undergo a rapid and strong activation that triggers an innate-like alarm state that can lead to activation of dendritic cells (DC). However, the interaction between skin Trm cells and DC in the context of antitumor immunity remains unexplored. Material and Methods: C57BL/6 mice received OT-I CD8+ T cells and were intradermally vaccinated with an ovalbumin (OVA)-encoding plasmid. After 4 weeks, circulating CD8+ T cells were depleted by injecting anti-CD8 antibody. Some mice were intradermally injected with OVA257-264 peptide. Others received PMEL-1 CD8+ T cells and were challenged with B16F10 or B16F10-OVA cells. DDC and CD8+ T cells were analyzed in skin and draining lymph nodes by flow cytometry. Then, mice were re-challenged with B16F10 in the contralateral flank. Results: Vaccination-induced OVA-specific skin Trm cells mediated the rejection of OVA-expressing, but not parental, B16F10 melanoma cells. OVA-specific activation of Trm cells induced maturation and migration to lymph nodes of cross-presenting CD103+ dermal DC (DDC). Interestingly, Trm cell-mediated rejection of B16F10-OVA melanoma lead to the generation of CD8+ T cell responses against melanoma-derived antigen GP100 and protection against B16F10 re-challenge. Discussion: Our results indicates that skin Trm cell-mediated rejection of melanoma cells enables DDC to initiate secondary CD8+ T cell responses against melanoma-derived antigens, further broadening antitumor immunity and controlling potential antigen-loss escape mutants.