Quantification of Early-Stage Myeloid-Derived Suppressor Cells in Cancer Requires Excluding Basophils
| Autor: | Jerry T. Wong, Tiffany R. Emmons, Kevin H. Eng, Anm Nazmul H. Khan, Brandon E. Smith, Kirsten B. Moysich, Scott I. Abrams, Kelly L. Singel, Kunle Odunsi, Brahm H. Segal, Jaron Mark, Emad Alqassim, Joseph D. Tario |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Immunology chemical and pharmacologic phenomena Basophil Basophil degranulation Article Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine parasitic diseases Ascites Biomarkers Tumor Tumor Cells Cultured Tumor Microenvironment medicine Humans Prospective Studies Retrospective Studies Ovarian Neoplasms Tumor microenvironment business.industry Myeloid-Derived Suppressor Cells Cancer hemic and immune systems Middle Aged Prognosis medicine.disease Basophils Survival Rate 030104 developmental biology medicine.anatomical_structure Case-Control Studies 030220 oncology & carcinogenesis Leukocytes Mononuclear Myeloid-derived Suppressor Cell Cancer research Female medicine.symptom business Ovarian cancer |
| Zdroj: | Cancer Immunol Res |
| ISSN: | 2326-6074 2326-6066 |
| Popis: | Myeloid derived suppressor cells (MDSC) are a heterogeneous group of immature cells that accumulate in the peripheral blood and tumor microenvironment and are barriers to cancer therapy. MDSCs serve as prognostic biomarkers and are targets for therapy. On the basis of surface markers, three subsets of MDSCs have been defined in humans: granulocytic, monocytic, and early stage (e-MDSC). The markers attributed to e-MDSCs overlap with those of basophils, which are rare circulating myeloid cells with unrecognized roles in cancer. Thus, we asked whether e-MDSCs in circulation and the tumor microenvironment include basophils. On average, 58% of cells with e-MDSC surface markers in blood and 36% in ascites from patients with ovarian cancer were basophils based on CD123high expression and cytology, whereas cells with immature features were rare. Circulating and ascites basophils did not suppress proliferation of stimulated T cells, a key feature of MDSCs. Increased accumulation of basophils and basogranulin, a marker of basophil degranulation, were observed in ascites compared to serum in patients with newly diagnosed ovarian cancer. Basophils recruited to the tumor microenvironment may exacerbate fluid accumulation by their release of proinflammatory granular constituents that promote vascular leakage. No significant correlation was observed between peripheral basophil counts and survival in patients with ovarian cancer. Our results suggest that studies in which e-MDSCs were defined solely by surface markers should be reevaluated to exclude basophils. Both immaturity and suppression are criteria to define e-MDSCs in future studies. |
| Databáze: | OpenAIRE |
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