Resident memory T cells in the skin mediate durable immunity to melanoma

Abstract

Tissue-resident memory T cells (TRM cells) have been widely characterized in infectious disease settings; however, their role in mediating immunity to cancer remains unknown. Here we report that skin-resident memory T cell responses to melanoma are generated naturally as a result of autoimmune vitiligo. Melanoma antigen-specific TRM cells resided predominantly in melanocyte-depleted hair follicles and were maintained without recirculation or replenishment from the lymphoid compartment. These cells expressed CD103, CD69, and CLA, but lacked PD-1 or LAG-3, and were capable of making IFN-γ. CD103 expression on CD8 T cells was required for establishment of TRM cells in skin, but was dispensable for vitiligo development. Importantly, CD103+ CD8 TRM cells were critical for protection against melanoma re-challenge. This work establishes that CD103-dependent TRM cells play a key role in perpetuating anti-tumor immunity.

Accumulation of CD103+ CD8+ T cells in a cutaneous melanoma micrometastasis

“…Importantly, the density of T RM cells within the tumor environment has been shown to predict for improved survival in a number of cancer types, including advanced‐stage melanoma . In line with this, recent reports have shown that T RM cells afford potent antitumor immunity in mouse models . Furthermore, we have recently demonstrated that T RM cells can promote cancer‐immune equilibrium in mouse skin by keeping dispersed melanoma cells dormant over extended periods of time .…”

“…15 In line with this, recent reports have shown that T RM cells afford potent antitumor immunity in mouse models. 10,13,[16][17][18] Furthermore, we have recently demonstrated that T RM cells can promote cancer-immune equilibrium in mouse skin by keeping dispersed melanoma cells dormant over extended periods of time. 19 Whether T RM cells have a similar function in maintaining tumor dormancy in humans, however, remains to be addressed.…”

Vitiligo as a skin memory disease: The need for early intervention with immunomodulating agents and a maintenance therapy to target resident memory T cells

“…T RM expressing CD49a were also observed both in the dermis and epidermis of vitiligo lesional skin and were characterized by production of IFNγ, perforin and granzyme B, notably when T RM cells were cultured in the presence of IL‐15, a cytokine that has been shown to be involved in T RM differentiation and maintenance. In line with the involvement of T RM in vitiligo, melanoma‐associated vitiligo supports T RM that can provide anti‐tumor immunity in vivo …”

Identification of CD49a+ CD8+ resident memory T cells in vitiligo‐like lesions associated with nivolumab treatment for melanoma

“…8 Another report revealed that CD49a+ CD103+ CD8+ T RM cells in human vitiligo vulgaris were poised for cytotoxic functions. In particular, CD49a+ CD103+ CD8+ T RM cells were present only in perilesional skin.…”