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Review
. 2021 May 21;10(6):1282.
doi: 10.3390/cells10061282.

The Interplay between the Immune and the Endocannabinoid Systems in Cancer

Mariantonia Braile  1   2 , Simone Marcella  1   2 , Gianni Marone  1   2   3 , Maria Rosaria Galdiero  1   2   3 , Gilda Varricchi  1   2   3 , Stefania Loffredo  1   2   3
Affiliations
Review

The Interplay between the Immune and the Endocannabinoid Systems in Cancer

Mariantonia Braile et al. Cells. .

Abstract

The therapeutic potential of Cannabis sativa has been recognized since ancient times. Phytocannabinoids, endocannabinoids and synthetic cannabinoids activate two major G protein-coupled receptors, subtype 1 and 2 (CB1 and CB2). Cannabinoids (CBs) modulate several aspects of cancer cells, such as apoptosis, autophagy, proliferation, migration, epithelial-to-mesenchymal transition and stemness. Moreover, agonists of CB1 and CB2 receptors inhibit angiogenesis and lymphangiogenesis in vitro and in vivo. Low-grade inflammation is a hallmark of cancer in the tumor microenvironment (TME), which contains a plethora of innate and adaptive immune cells. These cells play a central role in tumor initiation and growth and the formation of metastasis. CB2 and, to a lesser extent, CB1 receptors are expressed on a variety of immune cells present in TME (e.g., T cells, macrophages, mast cells, neutrophils, NK cells, dendritic cells, monocytes, eosinophils). The activation of CB receptors modulates a variety of biological effects on cells of the adaptive and innate immune system. The expression of CB2 and CB1 on different subsets of immune cells in TME and hence in tumor development is incompletely characterized. The recent characterization of the human cannabinoid receptor CB2-Gi signaling complex will likely aid to design potent and specific CB2/CB1 ligands with therapeutic potential in cancer.

Keywords: angiogenesis; cancer; cannabis; endocannabinoid system; immune cells; tumor microenvironment.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of the potential anticancer effects of endocannabinoids, phytocannabinoids and synthetic cannabinoids through the activation of CB1/CB2, GPR55 and TRPV1/TRPV2 receptors.
Figure 2
Figure 2
Schematic representation of cells of innate and adaptive immune system expressing CB receptors in the tumor microenvironment.
See this image and copyright information in PMC

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