Extracellular Nicotinamide Phosphoribosyltransferase neutralisation harnesses T cell responses in breast cancer by repressing the PD-1/PD-L1 axis

Nicotinamide phosphoribosyltransferase (NAMPT) is a key intracellular enzyme that particulates in NAD homeostasis but is also a released cytokine (eNAMPT) that is found elevated in inflammatory conditions and in cancer. Given that in breast cancer patients, eNAMPT has been found elevated and its levels correlate with prognosis and staging, we set to investigate the effect of its neutralization with a specific monoclonal antibody. Neutralization of eNAMPT with C269 led to a decreased tumour size and reduced number of metastases. RNAseq and functional assays showed that eNAMPT controlled the PD-L1/PD-1 axis and its neutralization led to a restoration of antitumoural immune responses. These studies are highly consistent with eNAMPT as a novel immunotherapeutic target for triple negative breast cancer. Overall design: We used 5 replicates of 6 samples (4T1 CTRL, 4T1 C269, CD4 CTRL, CD4 C269, CD8 CTRL, CD8 C269) using Illumina NextSeq 500