Single-cell transcriptomic profiling of FAP-CD40 and PD1-IL2v combination therapy in murine KPC pancreatic tumors
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.