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

Autor:	Schiferle EB; Center for Cancer Immunology and Cutaneous Biology Research Center, Department of Dermatology, Center for Cancer Research, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA., Cheon SY; Center for Cancer Immunology and Cutaneous Biology Research Center, Department of Dermatology, Center for Cancer Research, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA., Ham S; Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Yuseong Gu, Daejeon, South Korea., Son HG; Center for Cancer Immunology and Cutaneous Biology Research Center, Department of Dermatology, Center for Cancer Research, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA., Messerschmidt JL; Center for Cancer Immunology and Cutaneous Biology Research Center, Department of Dermatology, Center for Cancer Research, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA., Lawrence DP; Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA., Cohen JV; Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA., Flaherty KT; Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA., Moon JJ; Center for Immunology and Inflammatory Diseases and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA., Lian CG; Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA., Sullivan RJ; Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA., Demehri S; Center for Cancer Immunology and Cutaneous Biology Research Center, Department of Dermatology, Center for Cancer Research, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. sdemehri1@mgh.harvard.edu.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2021 Jun 23; Vol. 7 (26). Date of Electronic Publication: 2021 Jun 23 (Print Publication: 2021).
DOI:	10.1126/sciadv.abg4498
Abstrakt:	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. (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)
Databáze:	MEDLINE
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