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Targeting immune suppressing myeloid-derived suppressor cells in oncology

Targeting immune suppressing myeloid-derived suppressor cells in oncology,10.1016/j.critrevonc.2010.02.004,Critical Reviews in Oncology Hematology,Joh

Targeting immune suppressing myeloid-derived suppressor cells in oncology   (Citations: 2)
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Emerging data suggests that host immune cells with a suppressive phenotype represent a significant hurdle to successful therapy for metastatic cancer. Among the suppressor cells, T regulatory cells (Treg) and myeloid-derived suppressor cells (MDSC) are significantly increased in hosts with advanced malignancies. MDSC mediate the suppression of the tumor antigen-specific T cell response through the induction of T cell anergy and the development of Treg in tumor-bearing mice. These results provide robust evidence of an in vivo immunoregulatory function of MDSC in the establishment of tumor antigen-specific tolerance and the development of Treg in tumor-bearing hosts. To achieve effective anti-tumor immunity, tumor-induced immunosuppression must be reversed. Our preliminary results indicate that c-kit ligand (stem cell factor) expressed by tumor cells may be required for MDSC accumulation in tumor-bearing mice, and that blocking the c-kit ligand/c-kit receptor interaction can prevent the development of Treg and reverse immune tolerance induced by MDSC. Since c-kit can be readily inhibited by several small molecule inhibitors including imatinib, sunitinib and dasatinib, targeting immune suppressing cells can be readily accomplished in the clinic.
Journal: Critical Reviews in Oncology Hematology - CRIT REV ONCOL HEMATOL , vol. 77, no. 1, pp. 12-19, 2011
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