1. CD38+ M-MDSC expansion characterizes a subset of advanced colorectal cancer patients.
- Author
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Karakasheva TA, Dominguez GA, Hashimoto A, Lin EW, Chiu C, Sasser K, Lee JW, Beatty GL, Gabrilovich DI, and Rustgi AK
- Subjects
- ADP-ribosyl Cyclase 1 immunology, Adult, Aged, Animals, Antibodies, Monoclonal, Colorectal Neoplasms immunology, Esophageal Neoplasms immunology, Female, Humans, Immunosuppressive Agents pharmacology, Lymphocytes, Male, Membrane Glycoproteins immunology, Mice, Middle Aged, Monocytes, Pennsylvania, ADP-ribosyl Cyclase 1 metabolism, Colorectal Neoplasms metabolism, Esophageal Neoplasms metabolism, Leukocytes, Mononuclear metabolism, Membrane Glycoproteins metabolism, Myeloid-Derived Suppressor Cells metabolism, Neutrophils metabolism
- Abstract
Background: Myeloid-derived suppressor cells (MDSCs) are a population of immature immune cells with several protumorigenic functions. CD38 is a transmembrane receptor-ectoenzyme expressed by MDSCs in murine models of esophageal cancer. We hypothesized that CD38 could be expressed on MDSCs in human colorectal cancer (CRC), which might allow for a new perspective on therapeutic targeting of human MDSCs with anti-CD38 monoclonal antibodies in this cancer., Methods: Blood samples were collected from 41 CRC patients and 8 healthy donors, followed by peripheral blood mononuclear cell (PBMC) separation. Polymorphonuclear (PMN-) and monocytic (M-) MDSCs and CD38 expression levels were quantified by flow cytometry. The immunosuppressive capacity of M-MDSCs from 10 CRC patients was validated in a mixed lymphocyte reaction (MLR) assay., Results: A significant expansion of CD38+ M-MDSCs and a trend of expansion of CD38+ PMN-MDSCs (accompanied by a trend of increased CD38 expression on both M- and PMN-MDSCs) were observed in PBMCs of CRC patients when compared with healthy donors. The CD38+ M-MDSCs from CRC patients were found to be immunosuppressive when compared with mature monocytes. CD38+ M- and PMN-MDSC frequencies were significantly higher in CRC patients who previously received treatment when compared with treatment-naive patients., Conclusions: This study provides a rationale for an attempt to target M-MDSCs with an anti-CD38 monoclonal antibody in metastatic CRC patients., Funding: NCI P01-CA14305603, the American Cancer Society, Scott and Suzi Lustgarten Family Colon Cancer Research Fund, Hansen Foundation, and Janssen Research and Development.
- Published
- 2018
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