The ART of tumor immune escape

Erik Wennerberg; Sumit Mukherjee; Ricardo M Sainz; Brendon M Stiles

doi:10.1080/2162402X.2022.2076310

The ART of tumor immune escape

Oncoimmunology. 2022 May 14;11(1):2076310. doi: 10.1080/2162402X.2022.2076310. eCollection 2022.

Authors

Erik Wennerberg¹, Sumit Mukherjee², Ricardo M Sainz¹, Brendon M Stiles²

Affiliations

¹ Division of Radiotherapy and Imaging, Institute of Cancer Research, London, UK.
² Department of Cardiothoracic and Vascular Surgery, Albert Einstein College of Medicine, Bronx, NY, USA.

Abstract

We recently identified the adenosine-5'-diphosphate (ADP)-ribosyltransferase-1 (ART1) as a novel immune checkpoint expressed by cancer cells. ART1 utilizes free nicotinamide adenine dinucleotide (NAD⁺) in the tumor microenvironment (TME) to mono-ADP-ribosylate (MARylate) the P2X7 receptor (P2X7R) on CD8 T cells, resulting in NAD-induced cell death (NICD) and tumor immune resistance. This process is blocked by therapeutic antibody targeting of ART1.

Keywords: CD38; CD8 T cells; NAD-induced cell death; P2X7 receptor; immune escape; lung cancer; mono-ADP-ribosylation.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

ADP Ribose Transferases* / metabolism
Adenosine Diphosphate
Cell Death
NAD* / metabolism
NAD* / pharmacology
Tumor Escape

Substances

NAD
Adenosine Diphosphate
ADP Ribose Transferases

Grants and funding

Funding was provided from the Lung Cancer Research Foundation and the Department of Defense CDMRP Lung Cancer Research Program.