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.