MCRS1 sensitizes pancreatic cancer to T cell immunity [scRNA]

Pancreatic cancer is one of the deadliest cancers in humans and is yet refractory to immunotherapy. Identifying factors that can sensitize pancreatic cancer to immune cells may thus hold the key to improving immunotherapy efficacy. Herein, by pooled CRISPR activation screening, we find that the transcriptional regulator Mcrs1 (Microspherule protein 1) is pivotal to the immune sensitivity of pancreatic cancer cells, with elevated Mcrs1 expression inducing enhanced immune responses and tumor suppression in mice. Overall design: The tumor-infiltrating lymphocytes in Mcrs1ox or control tumors were isolated with collangenase digestion, followed by centrifugation in a discontinuous Percoll density gradient. TCRb+ CD90.2+ cells were sorted with a FACSAria Fusion Flow Cytometer, with dead cells excluded as DAPI+. Sorted cells were then stained with the Biolegend TotalSeq Hashtags for single cell RNA-seq and TCR-seq.