PMID- 34162549
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210814
IS  - 2375-2548 (Electronic)
IS  - 2375-2548 (Linking)
VI  - 7
IP  - 26
DP  - 2021 Jun
TI  - Rejection of benign melanocytic nevi by nevus-resident CD4(+) T cells.
LID - 10.1126/sciadv.abg4498 [doi]
LID - eabg4498
AB  - 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.
CI  - Copyright (c) 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).
FAU - Schiferle, Erik B
AU  - Schiferle EB
AUID- ORCID: 0000-0002-3998-7530
AD  - 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.
FAU - Cheon, Se Yun
AU  - Cheon SY
AUID- ORCID: 0000-0002-8527-8938
AD  - 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.
FAU - Ham, Seokjin
AU  - Ham S
AUID- ORCID: 0000-0002-6950-2848
AD  - Department of Biological Sciences, Korea Advanced Institute of Science and 
      Technology, Yuseong Gu, Daejeon, South Korea.
FAU - Son, Heehwa G
AU  - Son HG
AD  - 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.
FAU - Messerschmidt, Jonathan L
AU  - Messerschmidt JL
AUID- ORCID: 0000-0002-6132-7256
AD  - 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.
FAU - Lawrence, Donald P
AU  - Lawrence DP
AD  - Division of Hematology and Oncology, Department of Medicine, Massachusetts 
      General Hospital and Harvard Medical School, Boston, MA 02114, USA.
FAU - Cohen, Justine V
AU  - Cohen JV
AD  - Division of Hematology and Oncology, Department of Medicine, Massachusetts 
      General Hospital and Harvard Medical School, Boston, MA 02114, USA.
FAU - Flaherty, Keith T
AU  - Flaherty KT
AUID- ORCID: 0000-0002-3402-0478
AD  - Division of Hematology and Oncology, Department of Medicine, Massachusetts 
      General Hospital and Harvard Medical School, Boston, MA 02114, USA.
FAU - Moon, James J
AU  - Moon JJ
AUID- ORCID: 0000-0001-8246-931X
AD  - 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.
FAU - Lian, Christine G
AU  - Lian CG
AUID- ORCID: 0000-0003-4626-1612
AD  - Program in Dermatopathology, Department of Pathology, Brigham and Women's 
      Hospital and Harvard Medical School, Boston, MA 02115, USA.
FAU - Sullivan, Ryan J
AU  - Sullivan RJ
AUID- ORCID: 0000-0001-5344-6645
AD  - Division of Hematology and Oncology, Department of Medicine, Massachusetts 
      General Hospital and Harvard Medical School, Boston, MA 02114, USA.
FAU - Demehri, Shadmehr
AU  - Demehri S
AUID- ORCID: 0000-0002-7913-2641
AD  - 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.
LA  - eng
GR  - DP5 OD021353/OD/NIH HHS/United States
GR  - R01 AI107020/AI/NIAID NIH HHS/United States
GR  - R01 AR076013/AR/NIAMS NIH HHS/United States
PT  - Journal Article
DEP - 20210623
PL  - United States
TA  - Sci Adv
JT  - Science advances
JID - 101653440
SB  - IM
PMC - PMC8221625
EDAT- 2021/06/25 06:00
MHDA- 2021/06/25 06:01
PMCR- 2021/06/23
CRDT- 2021/06/24 05:40
PHST- 2021/01/07 00:00 [received]
PHST- 2021/05/10 00:00 [accepted]
PHST- 2021/06/24 05:40 [entrez]
PHST- 2021/06/25 06:00 [pubmed]
PHST- 2021/06/25 06:01 [medline]
PHST- 2021/06/23 00:00 [pmc-release]
AID - 7/26/eabg4498 [pii]
AID - abg4498 [pii]
AID - 10.1126/sciadv.abg4498 [doi]
PST - epublish
SO  - Sci Adv. 2021 Jun 23;7(26):eabg4498. doi: 10.1126/sciadv.abg4498. Print 2021 Jun.