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

Brian T. Malik; Katelyn T. Byrne; Jennifer L. Vella; Peisheng Zhang; Tamer B. Shabaneh; Shannon M. Steinberg; Aleksey K. Molodtsov; Jacob S. Bowers; Christina V. Angeles; Chrystal M. Paulos; Yina H. Huang; Mary Jo Turk

doi:10.1126/sciimmunol.aam6346

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

Brian T. Malik, Katelyn T. Byrne, Jennifer L. Vella, Peisheng Zhang, Tamer B. Shabaneh, Shannon M. Steinberg, Aleksey K. Molodtsov, Jacob S. Bowers, Christina V. Angeles, Chrystal M. Paulos, Yina H. Huang, Mary Jo Turk

Research output: Contribution to journal › Article › peer-review

197 Scopus citations

Abstract

Tissue-resident memory T (T_RM) 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 T_RM 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- (interferon-). CD103 expression on CD8 T cells was required for the establishment of T_RM cells in the skin but was dispensable for vitiligo development. CD103⁺ CD8 T_RM cells were critical for protection against melanoma rechallenge. This work establishes that CD103-dependent T_RM cells play a key role in perpetuating antitumor immunity.

Original language	English (US)
Article number	eaam6346
Journal	Science Immunology
Volume	2
Issue number	10
DOIs	https://doi.org/10.1126/sciimmunol.aam6346
State	Published - 2017
Externally published	Yes

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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title = "Resident memory T cells in the skin mediate durable immunity to melanoma",

abstract = "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- (interferon-). 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 = "Malik, {Brian T.} and Byrne, {Katelyn T.} and Vella, {Jennifer L.} and Peisheng Zhang and Shabaneh, {Tamer B.} and Steinberg, {Shannon M.} and Molodtsov, {Aleksey K.} and Bowers, {Jacob S.} and Angeles, {Christina V.} and Paulos, {Chrystal M.} and Huang, {Yina H.} and Turk, {Mary Jo}",

note = "Publisher Copyright: 2017 {\textcopyright} The Authors.",

year = "2017",

doi = "10.1126/sciimmunol.aam6346",

language = "English (US)",

volume = "2",

journal = "Science Immunology",

issn = "2470-9468",

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T1 - Resident memory T cells in the skin mediate durable immunity to melanoma

AU - Malik, Brian T.

AU - Byrne, Katelyn T.

AU - Vella, Jennifer L.

AU - Zhang, Peisheng

AU - Shabaneh, Tamer B.

AU - Steinberg, Shannon M.

AU - Molodtsov, Aleksey K.

AU - Bowers, Jacob S.

AU - Angeles, Christina V.

AU - Paulos, Chrystal M.

AU - Huang, Yina H.

AU - Turk, Mary Jo

PY - 2017

Y1 - 2017

N2 - 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- (interferon-). 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.

AB - 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- (interferon-). 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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Resident memory T cells in the skin mediate durable immunity to melanoma

Abstract

ASJC Scopus subject areas

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