Rejection of benign melanocytic nevi by nevus-resident CD4(+) T cells

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Melanoma and melanocytic nevi harbor shared lineage-specific antigens and oncogenic mutations. Yet, the relationship between the immune system and melanocytic nevi is unclear. Using a patient-derived xenograft (PDX) model, we found that 81.8% of the transplanted nevi underwent spontaneous regression, while peripheral skin remained intact. Nevus-resident CD4(+) T helper 1 cells, which exhibited a massive clonal expansion to melanocyte-specific antigens, were responsible for nevus rejection. Boosting regulatory T cell suppressive function with low-dose exogenous human interleukin-2 injection or treatment with a human leukocyte antigen (HLA) class II-blocking antibody prevented nevus rejection. Notably, mice with rejected nevus PDXs were protected from melanoma tumor growth. We detected a parallel CD4(+) T cell-dominant immunity in clinically regressing melanocytic nevi. These findings reveal a mechanistic explanation for spontaneous nevus regression in humans and posit the activation of nevus-resident CD4(+) effector T cells as a novel strategy for melanoma immunoprevention and treatment.
Publisher
AMER ASSOC ADVANCEMENT SCIENCE
Issue Date
2021-06
Language
English
Article Type
Article
Citation

SCIENCE ADVANCES, v.7, no.26

ISSN
2375-2548
DOI
10.1126/sciadv.abg4498
URI
http://hdl.handle.net/10203/286570
Appears in Collection
RIMS Journal Papers
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