Next Article in Journal
Multicenter Analysis of Treatment Outcomes for Systemic Therapy in Well Differentiated Grade 3 Neuroendocrine Tumors (NET G3)
Next Article in Special Issue
New Targeted Therapies and Immunotherapies for Locally Advanced Periocular Malignant Tumours: Towards a New ‘Eye-Sparing’ Paradigm?
Previous Article in Journal
CD80 Expression on Tumor Cells Alters Tumor Microenvironment and Efficacy of Cancer Immunotherapy by CTLA-4 Blockade
Previous Article in Special Issue
Find the Flame: Predictive Biomarkers for Immunotherapy in Melanoma
Article

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

1
Institute of Pathology, University of Bern, 3008 Bern, Switzerland
2
Graduate School GCB, University of Bern, 3012 Bern, Switzerland
3
Institute of Biochemistry and Molecular Medicine, University of Bern, 3012 Bern, Switzerland
*
Author to whom correspondence should be addressed.
Academic Editor: Kavita Y. Sarin
Cancers 2021, 13(8), 1934; https://doi.org/10.3390/cancers13081934
Received: 19 March 2021 / Revised: 12 April 2021 / Accepted: 13 April 2021 / Published: 16 April 2021
(This article belongs to the Special Issue Molecular Mechanisms of Skin Cancer)
In this study we investigated the role of cannabinoid receptor 2 (CB2R) on immune cells in melanoma and found significantly improved overall survival in patients with high intra-tumoral CB2R gene expression. In human melanoma, CB2R is predominantly expressed in B cells, as shown using a previously published single-cell RNA sequencing (scRNA-seq) dataset and by performing RNAscope. In a murine melanoma model, tumor growth was enhanced in CB2R-deficient mice. In-depth analysis of tumor-infiltrating lymphocytes using scRNA-seq showed less differentiated B cells in CB2R-deficient tumors, favoring the induction of regulatory T cells (Treg) and an immunosuppressive tumor microenvironment. Taken together, these data indicate a central role of CB2R on B cells in regulating tumor immunity. These results contribute to the understanding of the role of CB2R in tumor immunity and facilitate the development of new CB2R-targeted anti-cancer drugs.
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 Cb2r−/− 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. View Full-Text
Keywords: cannabinoid receptor type-2; CB2R; endocannabinoid system; regulatory B cells; melanoma cannabinoid receptor type-2; CB2R; endocannabinoid system; regulatory B cells; melanoma
Show Figures

Graphical abstract

MDPI and ACS Style

Gruber, T.; Robatel, S.; Kremenovic, M.; Bäriswyl, L.; Gertsch, J.; Schenk, M. Cannabinoid Receptor Type-2 in B Cells Is Associated with Tumor Immunity in Melanoma. Cancers 2021, 13, 1934. https://doi.org/10.3390/cancers13081934

AMA Style

Gruber T, Robatel S, Kremenovic M, Bäriswyl L, Gertsch J, Schenk M. Cannabinoid Receptor Type-2 in B Cells Is Associated with Tumor Immunity in Melanoma. Cancers. 2021; 13(8):1934. https://doi.org/10.3390/cancers13081934

Chicago/Turabian Style

Gruber, Thomas, Steve Robatel, Mirela Kremenovic, Lukas Bäriswyl, Jürg Gertsch, and Mirjam Schenk. 2021. "Cannabinoid Receptor Type-2 in B Cells Is Associated with Tumor Immunity in Melanoma" Cancers 13, no. 8: 1934. https://doi.org/10.3390/cancers13081934

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop