Tumour immune escape via P2X7 receptor signalling

Ricardo M Sainz; Jorge Humberto Rodriguez-Quintero; Maria Constanza Maldifassi; Brendon M Stiles; Erik Wennerberg

doi:10.3389/fimmu.2023.1287310

Tumour immune escape via P2X7 receptor signalling

Front Immunol. 2023 Oct 30:14:1287310. doi: 10.3389/fimmu.2023.1287310. eCollection 2023.

Authors

Ricardo M Sainz¹, Jorge Humberto Rodriguez-Quintero², Maria Constanza Maldifassi², Brendon M Stiles², Erik Wennerberg¹

Affiliations

¹ Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, United Kingdom.
² Department of Cardiovascular and Thoracic Surgery, Albert Einstein College of Medicine, Montefiore Health System, Bronx, NY, United States.

Abstract

While P2X7 receptor expression on tumour cells has been characterized as a promotor of cancer growth and metastasis, its expression by the host immune system is central for orchestration of both innate and adaptive immune responses against cancer. The role of P2X7R in anti-tumour immunity is complex and preclinical studies have described opposing roles of the P2X7R in regulating immune responses against tumours. Therefore, few P2X7R modulators have reached clinical testing in cancer patients. Here, we review the prognostic value of P2X7R in cancer, how P2X7R have been targeted to date in tumour models, and we discuss four aspects of how tumours skew immune responses to promote immune escape via the P2X7R; non-pore functional P2X7Rs, mono-ADP-ribosyltransferases, ectonucleotidases, and immunoregulatory cells. Lastly, we discuss alternative approaches to offset tumour immune escape via P2X7R to enhance immunotherapeutic strategies in cancer patients.

Keywords: ART1; CD38; CD39; P2X7 receptor; cancer immunotherapy; tumour immune escape; tumour microenvironment.

Publication types

Review
Research Support, Non-U.S. Gov't
Comment

MeSH terms

Humans
Neoplasms*
Receptors, Purinergic P2X7
Signal Transduction
Tumor Escape*

Substances

Receptors, Purinergic P2X7

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the ICR/RM CRUK RadNet Centre of Excellence.