Cannabinoid Receptor Type-2 in B Cells Is Associated with Tumor Immunity in Melanoma

Agents targeting the endocannabinoid system (ECS) have gained attention as potential cancer treatments. Given recent evidence that cannabinoid receptor 2 (CB2R) regulates lymphocyte development and inflammation, we performed studies on CB2R in the immune response against melanoma. Analysis of The Ca...

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Bibliographic Details
Published in:Cancers 2021-04, Vol.13 (8), p.1934
Main Authors: Gruber, Thomas, Robatel, Steve, Kremenovic, Mirela, Bäriswyl, Lukas, Gertsch, Jürg, Schenk, Mirjam
Format: Article
Language:English
Subjects:
Antibodies
Antitumor agents
Cancer
Cannabinoid CB2 receptors
Cannabinoids
Cell differentiation
Cloning
Drug delivery
Drug development
Endocannabinoid system
Gene expression
Genomes
Immunity
Immunoregulation
Immunosuppressive agents
Immunotherapy
Inflammation
Lymphocytes B
Lymphocytes T
Melanoma
Metastases
Phenotypes
Skin cancer
Tumor microenvironment
Tumor-infiltrating lymphocytes
Tumors
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Summary:Agents targeting the endocannabinoid system (ECS) have gained attention as potential cancer treatments. Given recent evidence that cannabinoid receptor 2 (CB2R) regulates lymphocyte development and inflammation, we performed studies on CB2R in the immune response against melanoma. Analysis of The Cancer Genome Atlas (TCGA) data revealed a strong positive correlation between CB2R expression and survival, as well as B cell infiltration in human melanoma. In a murine melanoma model, CB2R expression reduced the growth of melanoma as well as the B cell frequencies in the tumor microenvironment (TME), compared to CB2R-deficient mice. In depth analysis of tumor-infiltrating B cells using single-cell RNA sequencing suggested a less differentiated phenotype in tumors from mice. Thus, in this study, we demonstrate for the first time a protective, B cell-mediated role of CB2R in melanoma. This gained insight might assist in the development of novel, CB2R-targeted cancer therapies.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13081934