Abstract 3464: Dynamics of resident memory (Trm) cell responses between skin and draining lymph nodes during primary and recall responses to melanoma

Abstract

Abstract Tissue resident memory (TRM) cells reside durably in tissues where they serve as a vital component of protective anti-tumor immunity. In mice, TRM cells are defined by their expression of tissue retention markers such as CD69 and CD103, and lack of egress markers such as CD62L, CCR7 and S1PR1. We previously showed that depletion of regulatory T cells induces the generation of protective CD8 Trm cells in skin and draining LNs of B16 melanoma tumor-excised mice. While tumor specific Trm cells were shown to stably reside in tissues at steady state, little is known about their migration between tissue compartments and circulation during primary and recall responses to melanoma. Using gp100-specific transgenic pmel CD8 T cells expressing a Kaede-GFP photoconvertible marker, we investigated the trafficking patterns of tumor Ag specific CD8+ T-cells that were labeled in situ by exposure to UV light in the skin. During primary tumor growth, we observed pronounced movement of antigen-experienced pmel cells through skin to tumor-draining LNs. This trafficking behavior could be inhibited by treatment with FTY720, indicating its S1PR-dependence. Such movement was no longer evident at memory timepoints. However, re-challenge with B16 cells in the dermis induced rapid pmel T cell egress to both LNs and circulation. Recallenge-mediated Trm cell skin egress was confirmed using anti-Thy1.1 monoclonal antibody to deplete circulating and lymphoid memory, while preserving skin TRM. Here we found that skin TRM proliferate and transiently increase expression of Tbet, but go on to generate a durable secondary Trm response in lymph nodes. These data highlight T cell movement between tissues during Trm programming and recall responses to cancer, and shed light on a potential mechanism for the generation TRM populations in tumor-draining lymph nodes. Moreover, our results highlight the potential for retrograde movement of Trm responses from peripheral tissue reservoirs to participate more broadly in systemic anti-tumor immunity. Citation Format: Cameron Messier, Nikhil Khatwani, Aaron Hawkes, Yuyang (Poppy) Huang, Mary Jo Turk. Dynamics of resident memory (Trm) cell responses between skin and draining lymph nodes during primary and recall responses to melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3464.