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

BT Malik, KT Byrne, JL Vella, P Zhang… - Science …, 2017 - science.org
BT Malik, KT Byrne, JL Vella, P Zhang, TB Shabaneh, SM Steinberg, AK Molodtsov…
Science immunology, 2017science.org
Tissue-resident memory T (TRM) cells have been widely characterized in infectious disease
settings; however, their role in mediating immunity to cancer remains unknown. 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 …
Tissue-resident memory T (TRM) cells have been widely characterized in infectious disease settings; however, their role in mediating immunity to cancer remains unknown. 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 (cutaneous lymphocyte antigen), but lacked PD-1 (programmed cell death protein–1) or LAG-3 (lymphocyte activation gene–3), and were capable of making IFN-γ (interferon-γ). CD103 expression on CD8 T cells was required for the establishment of TRM cells in the skin but was dispensable for vitiligo development. CD103+ CD8 TRM cells were critical for protection against melanoma rechallenge. This work establishes that CD103-dependent TRM cells play a key role in perpetuating antitumor immunity.
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