Single-cell RNA-sequence reveals the transcriptional dynamics of tumor immune microenvironment by autophagy inhibition in cancer cells

In this study, we investigated the impact of autophagy inhibition in cancer cell on the tumor immune microenvironment (TIME) of orthotopic syngeneic pancreatic ductal adenocarcinoma (PDAC) tumors. Dendritic cells (DCs) in the cancer cell autophagy inhibited tumors showed significantly higher expression of genes related to DC functions such as antigen-presentation, migration, IFN response, compared to control tumors. Our results indicate that autophagy inhibition in cancer cells induce the enhancement of adoptive tumor immunity via DC activation in PDAC. Overall design: Mouse PDAC cell lines were established from the primary PDAC tumors of KrasG12D/+, Trp53R172H/+, Pdx-1-Cre (KPC) mice. Autophagy-deficient KPC cells were generated by transfection with shRNAs targeting the autophagy-related gene, Atg7. KPC shNC / KPC shATG7 were transplanted into the pancreas of C57BL/6 mice, and we compared the transcriptional difference between the orthotopic syngeneic PDAC tumors transplanted KPC shNC or KPC shATG7. 1 sample integrated from 3 orthotopic syngeneic PDAC tumors transplanted KPC shNC. 1 sample integrated from 3 orthotopic syngeneic PDAC tumors transplanted KPC shATG7.