1. Deciphering the Crosstalk Between Myeloid-Derived Suppressor Cells and Regulatory T Cells in Pancreatic Ductal Adenocarcinoma.
- Author
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Siret C, Collignon A, Silvy F, Robert S, Cheyrol T, André P, Rigot V, Iovanna J, van de Pavert S, Lombardo D, Mas E, and Martirosyan A
- Subjects
- Animals, Biomarkers, Carcinoma, Pancreatic Ductal pathology, Cell Line, Tumor, Humans, Immunomodulation, Immunophenotyping, Lymphocytes, Tumor-Infiltrating, Mice, Myeloid-Derived Suppressor Cells pathology, T-Lymphocytes, Regulatory pathology, Tumor Microenvironment genetics, Tumor Microenvironment immunology, Xenograft Model Antitumor Assays, Carcinoma, Pancreatic Ductal etiology, Carcinoma, Pancreatic Ductal metabolism, Cell Communication immunology, Myeloid-Derived Suppressor Cells immunology, Myeloid-Derived Suppressor Cells metabolism, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory metabolism
- Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with rising incidence and a remarkable resistance to current therapies. The reasons for this therapeutic failure include the tumor's extensive infiltration by immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs). By using light sheet fluorescent microscopy, we identified here direct interactions between these major immunoregulatory cells in PDAC. The in vivo depletion of MDSCs led to a significant reduction in Tregs in the pancreatic tumors. Through videomicroscopy and ex vivo functional assays we have shown that (i) MDSCs are able to induce Treg cells in a cell-cell dependent manner; (ii) Treg cells affect the survival and/or the proliferation of MDSCs. Furthermore, we have observed contacts between MDSCs and Treg cells at different stages of human cancer. Overall our findings suggest that interactions between MDSCs and Treg cells contribute to PDAC immunosuppressive environment., (Copyright © 2020 Siret, Collignon, Silvy, Robert, Cheyrol, André, Rigot, Iovanna, van de Pavert, Lombardo, Mas and Martirosyan.)
- Published
- 2020
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