P2 purinergic receptor expression and function in tumor-related immune cells

Abstract

P2 purinergic receptor expression is dysregulated in multiple cancer subtypes and is associated with worse outcomes. Studies identify roles for P2 purinergic receptors in tumor cells that drive disease aggressiveness. There is also sufficient evidence that P2 purinergic receptor expression within the tumor microenvironment (TME) is critical for disease initiation and progression. Immune cells constitute a significant component of the TME and display both tumorigenic and anti-tumorigenic potential. Studies pre-dating the investigation of P2 purinergic receptors in cancer identify P2 receptor expression on multiple immune cells including macrophages, neutrophils, T-cells, and dendritic cells; all of which are implicated in tumor initiation, tumor promotion, or response to treatment. Herein, we discuss P2 purinergic receptor expression and function in tumor-related immune cells. We provide a rationale for further investigations of P2 purinergic receptors within the TME to better define the mechanistic pathways of inflammation-mediate tumorigenesis and explore P2 purinergic receptors as potential targets for novel immunotherapeutic approaches.

Keywords: Immune cells; Macrophages; Neutrophils; P2 purinergic receptor; T-cells; Tumor microenvironment.

Fig. 1

P2Y purinergic receptors on immune cells influence tumor growth, metastasis, angiogenesis, and immune cell phagocytosis, cytotoxicity, and tissue infiltration

Fig. 2

P2X purinergic receptors on immune cells influence tumor growth, angiogenesis, immune cell viability, tissue infiltration, phagocytosis, and T-cell recruitment