Abstract
Pancreatic ductal adenocarcinoma (PDAC) has been recognized as a immunologic-cold tumor. That partly explains why PDAC is not reactive to the currently available immunotherapies. Taking an insight into the characteristics of the PDAC immune microenvironment is fundamental to generate more effective strategies. Here, using mass cytometry (CyTOF), we identified the dynamic changes of tumor-infiltrating immune cells from healthy pancreas to spontaneous PDAC in the KPC mouse model. We observed two significant immunosuppressive stages with few T/B cell infiltrate. One is the acinar-ductal metaplasia (ADM) stage with transiently increased Tregs, the other is metastatic tumor stage with a large amount of myeloid suppressive cells. Surprisingly, tumors in an early stage still have a prominent presence of T/B cells. Trajectory analysis of monocyte/macrophage showed that the differentiation/activation branch of Ly-6C+ monocyte changes from a BST2+/MHC-II+ M1-like phenotype to an Arg-1+ M2-like phenotype over time during PDAC carcinogenesis and progression. The temporal immune characteristics were also confirmed in patient specimens. Our study demonstrates the coevolution of histopathology and immunology of developing PDAC and highlights that immunotherapy strategy exploitation should base on specific tumor stage.
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