Antigen-specific tissue-resident memory T cells (TRM; CD44hiCD62LloCD103hiCD69+CLA+/-) were established in the skin of mice developing autoimmune vitiligo. TRM provided protection against melanoma rechallenge, were self-sustaining without lymph node recirculation, and showed no markers of exhaustion, thus supporting exploration of TRM cells in cancer immunotherapy.
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-gamma (interferon-gamma). 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.
Author Info: (1) Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. (2) Department of Microbiology and Immunology, Geisel School of Medic
Author Info: (1) Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. (2) Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. Parker Institute for Cancer Immunotherapy and Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. (3) Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. (4) Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. (5) Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. (6) Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. (7) Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. (8) Departments of Microbiology and Immunology, and Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston, SC 29425, USA. (9) Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA. Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA. (10) Departments of Microbiology and Immunology, and Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston, SC 29425, USA. (11) Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA. (12) Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. mary.jo.turk@dartmouth.edu. Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA.
