Related Experiment Video
Updated: Nov 1, 2025
Patient Derived Cell Culture and Isolation of CD133+ Putative Cancer Stem Cells from Melanoma
Published on: March 13, 2013
Rejection of benign melanocytic nevi by nevus-resident CD4+ T cells
Erik B Schiferle1, Se Yun Cheon1, Seokjin Ham2
1Center 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.
Abstract:
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.
Insights
Immune cells called CD4+ T helper 1 cells drive spontaneous nevus regression by targeting melanocyte antigens. This immune response also protects against melanoma development.
Area of Science:
- Immunology
- Dermatology
- Oncology
Background:
- Melanoma and melanocytic nevi share antigens and mutations, but their immune system relationship is unknown.
- Understanding nevus-immune interactions may reveal insights into melanoma development and prevention.
Purpose of the Study:
- To investigate the immune system's role in melanocytic nevus regression.
- To explore the potential of targeting nevus immunity for melanoma prevention and treatment.
Main Methods:
- Utilized a patient-derived xenograft (PDX) model of melanocytic nevi.
- Analyzed T cell responses, including clonal expansion and phenotype.
- Intervened with interleukin-2 and HLA class II-blocking antibodies to assess impact on nevus regression.
- Evaluated protection against subsequent melanoma tumor growth in mice with rejected nevi.
Main Results:
- Transplanted nevi showed high rates (81.8%) of spontaneous regression in the PDX model.
- Nevus-resident CD4+ T helper 1 cells were identified as the key mediators of regression.
- Interventions boosting regulatory T cell function or blocking HLA class II prevented nevus rejection.
- Mice with rejected nevi exhibited protection against melanoma tumor growth.
Conclusions:
- CD4+ T cell-dominant immunity drives spontaneous regression of melanocytic nevi.
- This immune response offers protection against melanoma development.
- Activating nevus-resident CD4+ effector T cells represents a potential strategy for melanoma immunoprevention and therapy.
Related Concept Videos
01:27Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
01:22T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...
01:30Skin Cancer
Basal Cell Carcinoma (BCC): BCC is the most common type of skin cancer, accounting for about 80% of cases. It typically develops in...
01:29Immune Response Against Viral Pathogens
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...