Myeloid-derived suppressor cells as an immune parameter in patients with concurrent sunitinib and stereotactic body radiotherapy

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題名:	Myeloid-derived suppressor cells as an immune parameter in patients with concurrent sunitinib and stereotactic body radiotherapy
作者:	王陸海;Chen, Hui-Ming;Ma, Ge;Gildener-Leapman, Neil;Eisenstein, Samuel;Coakley, Brian A.;Ozao, Junko;Mandeli, John;Divino, Celia;Schwartz, Myron;Sung, Max;Ferris, Robert;Kao, Johnny;Wang, Lu-Hai;Pan, Ping-Ying;Ko, Eric C.;Chen, Shu-Hsia
貢獻者:	生醫理工學院生命科學系
關鍵詞:	Antineoplastic Agents - administration & dosage;CD11b Antigen - metabolism;CD4-Positive T-Lymphocytes - cytology;CD8-Positive T-Lymphocytes - cytology;Cell Proliferation;Cell Survival;Disease Progression;Flow Cytometry;Humans;Immune System;Immunosuppressive Agents - therapeutic use;Indoles - administration & dosage;Leukocytes, Mononuclear - cytology;Monocytes - cytology;Myeloid Cells - cytology;Neoplasm Metastasis;Neoplasms - immunology;Neoplasms - radiotherapy;Neoplasms - therapy;Phosphorylation;Pyrroles - administration & dosage;Radiosurgery;Sialic Acid Binding Ig-like Lectin 3 - metabolism;STAT3 Transcription Factor - metabolism;Treatment Outcome
日期:	2015-09-15
上傳時間:	2026-04-23 11:13:30 (UTC+8)
出版者:	American Association for Cancer Research Inc.;United States
摘要:	摘要： Purpose: The clinical effects of sunitinib on human myeloid-derived suppressor cell (MDSC) subsets and correlation of the T-cell–mediated immune responses and clinical outcomes in patients with oligometastases treated by stereotactic body radiotherapy (SBRT) have been evaluated. Experimental Design: The numbers of granulocytic and monocytic MDSC subsets, effector T cells, and regulatory T cells in the peripheral blood were evaluated pre- and post-sunitinib treatment and concurrent with SBRT. Correlations between MDSC, Treg, and T-cell responses and clinical outcomes were analyzed. Results: Patients with oligometastases of various cancer types had elevated granulocytic MDSC and certain subsets of monocytic MDSC population. Sunitinib treatment resulted in a significant reduction in monocytic MDSC, phosphorylated STAT3, and arginase levels in monocytic MDSC (CD33+CD14+CD16+), and an increase in T-cell proliferative activity in cancer patients. Interestingly, the effects of sunitinib on reducing the accumulation and immune-suppressive function of MDSC were significantly correlated with Treg reduction, in responders but not in nonresponding patients. SBRT synergized the therapeutic effects of sunitinib, especially as related to decreased numbers of monocytic MDSC, Treg, and B cells, and augmented Tbet expression in primary CD4 and CD8 T cells. These effects were not observed in patients receiving radiation therapy alone. Most interestingly, the responders, defined by sunitinib-mediated reduction in CD33+CD11b+ myeloid cell populations, tend to exhibit improved progression-free survival and cause-specific survival. Conclusions: Sunitinib treatment increased the efficacy of SBRT in patients with oligometastases by reversing MDSC and Treg-mediated immune suppression and may enhance cancer immune therapy to prevent tumor recurrence post-SBRT. Clin Cancer Res; 21(18); 4073–85. ©2015 AACR. 其他題名： Clin Cancer Res 出版者： United States 出版日期： 2015-09-15 出處： Clinical cancer research, 2015-09, Vol.21 (18), p.4073-4085 版權： 2015 American Association for Cancer Research. 識別號： ISSN: 1078-0432 識別號： ISSN: 1557-3265 識別號： EISSN: 1557-3265 識別號： DOI: 10.1158/1078-0432.CCR-14-2742 識別號： PMID: 25922428
顯示於類別:	[生命科學系] 期刊論文

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