Project description:Single-cell RNA-sequencing analyses were performed on unfractionated live cell mixtures from pancreatic tumors of KPC mice and wild-type mice to detect different myCAF subpopulations
Project description:Single-cell ATAC-sequencing analyses were performed on unfractionated live cell mixtures from pancreatic tumors of KPC mice and wild-type mice to better understand the epigenetic characteristics of different cell populations
Project description:A major barrier in pancreatic immunotherapy is the \"cold\" TME, characterized by T cell exclusion and a deficiency in cDC1s necessary for antigen presentation. Using the KPC mouse model, we found that while FAP-CD40 monotherapy only delayed tumor growth, combining it with PD1-IL2v induced robust regression. To elucidate the underlying mechanisms, we performed single-cell transcriptome analysis to compare the effects on T cell and myeloid populations across mono- and combination therapies. Our study revealed that the combination uniquely overcomes immune exclusion by generating dense intratumoral T cell-cDC1 clusters (TDCs). These TDCs drive anti-tumor immunity by sustaining local T cell proliferation within the parenchyma, independent of lymph node priming.
Project description:We harvested and sequenced the spontaneous pancreatic tumor generated by a 6-month-old KPC mouse (KrasLSL-G12D; Trp53LSL-R172H; Ptf1a-Cre).
Project description:Bulk RNA sequencing of sorted peri-pancreatic LN cDC1s from different stages of neoplastic development in the KPC mouse model of pancreatic adenocarcinoma.
