Skin Memory T-cells Confer Long-term Immunity To Melanoma

Unique immune cells, known as resident memory T cells, do an excellent job of preventing melanoma, researchers at Dartmouth University report in a newly published study.

Their finding stems from an investigation of why patients with melanoma who develop the autoimmune disease called vitiligo, have such good prognosis. Vitiligo is an autoimmune skin condition against normal healthy melanocytes, which causes the loss of skin pigmentation in blotches.

Using mouse models of melanoma and vitiligo, the research team found that resident memory T cells permanently reside in vitiligo-affected skin, where they kill melanoma cells. Although resident memory T cells were previously known to prevent skin viral infection, it was not known that they could fight tumors.

Resident Memory T Cells

The study shows for the first time that resident memory T cells are generated in response to a tumor, naturally as a result of autoimmune vitiligo, and serve a critical role in protecting against future tumors.

This discovery is unexpected, since T cells that fight cancer have previously been thought to reside only in immune organs such as spleen, lymph nodes, and blood and enter tumors from the blood. Study leader Mary Jo Turk, PhD, of Dartmouth’s Norris Cotton Cancer Center, said:

“Our studies challenge this long-held belief by showing that tumor-killing T cells already reside in skin, where they can rapidly respond and kill melanoma cells.”

Although these current studies are limited to mice, the presence of similar cells might explain why human patients with vitiligo are so well protected against melanoma and survive longer. Turk and her team plan to look for these cells in human patients.

“While we have shown that these T cells can kill melanoma in skin, we still need to determine whether they exist in other organs such as lung, where metastatic melanoma grows” said Turk. “Since our study identifies that resident memory T cells are critical for protection against tumors, and that T cells in skin provide long-term immunity to melanoma, the generation of such cells should be the goal of future cancer therapies.”

Melanoma antigen–specific TRM cells resided predominantly in melanocyte-depleted hair follicles and were maintained without recirculation or replenishment from the lymphoid compartment.

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
Resident memory T cells in the skin mediate durable immunity to melanoma
Science Immunology 14 Apr 2017: Vol. 2, Issue 10, eaam6346 DOI: 10.1126/sciimmunol.aam6346

Image: T cells in hair follicles of mice with vitiligo. Credit: Yina Huang

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