Cecile Alanio

"Deep immune profiling of pancreatic cancer patients reveals trafficking defect of effector-like T cells and retention in the spleen"

To investigate immune changes in pancreatic cancer, we profiled peripheral blood immune cells from newly-diagnosed pancreatic ductal adenocarcinoma (PDAC) patients and age-matched normal donors. Multi-platform profiling identified an altered landscape of immune cell subsets in the blood of untreated PDAC patients, with a prominent absence of CD45RA+CD27- terminally differentiated effector memory RA T cells (EMRA) in circulation. Absence of these cells from blood reflected accumulation in the spleens of newly diagnosed PDAC patients, indicating redistribution rather than loss of these cells. Mouse models of pancreatic cancer recapitulated this effect and identified a chemokine-dependent trafficking or retention of peripheral effector T cells in the spleen in context of pancreatic cancer. This effector CD8 T cell sequestration effect was at least partially dependent on the CXCL1/CXCR2 axis in mice and associated with preferential expression of CXCR2 by EMRA in human PDAC patient. These data identify a homing and/or sequestration of effector-like CD8 T cells in pancreatic cancer across species that may limit access of activated CD8 T cells to the tumor. These studies may have relevance for immunotherapy in PDAC patients including CAR T cells where migration to the solid tumor is essential and suggest strategies targeting CXCL1/CXCR2.