Rejection of benign melanocytic nevi by nevus-resident CD4+ T cells.
Erik B SchiferleSe Yun CheonSeokjin HamHeehwa G SonJonathan L MesserschmidtDonald P LawrenceJustine V CohenKeith T FlahertyJames J MoonChristine G LianRyan J SullivanShadhmer DemehriPublished in: Science advances (2021)
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.
Keyphrases
- low dose
- endothelial cells
- dendritic cells
- patient safety
- quality improvement
- regulatory t cells
- transcription factor
- immune response
- induced apoptosis
- type diabetes
- induced pluripotent stem cells
- high dose
- pluripotent stem cells
- combination therapy
- cell proliferation
- gene expression
- oxidative stress
- metabolic syndrome
- adipose tissue
- skeletal muscle
- ultrasound guided
- pi k akt
- peripheral blood
- wound healing
- wild type