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Abstract

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 

Author information

Chen HM1, Ma G1, Gildener-Leapman N2, Eisenstein S3, Coakley BA3, Ozao J3, Mandeli J4, Divino C5, Schwartz M5, Sung 

M6, Ferris R2, Kao J7, Wang LH8, Pan PY1, Ko EC9, Chen SH10.​

1Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York.

2Department of Otolaryngology and Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.

3Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York. Department of Surgery, Mount Sinai School of Medicine, New York, New York.

4Department of Preventive Medicine, Mount Sinai School of Medicine, New York, New York.

5Department of Surgery, Mount Sinai School of Medicine, New York, New York.

6Department of Medicine, Mount Sinai School of Medicine, New York, New York.

7Department of Radiation Oncology, Good Samaritan Hospital Medical Center, West Islip, New York.

8Institute of Molecular and Genomic Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 350, Taiwan.

9Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York. Department of Radiation Oncology, Mercy UC Davis Cancer Center, Merced, California. Department of Radiation Oncology, UC Davis Comprehensive Cancer Center, Sacramento, California. shu-hsia.chen@mssm.edu eric.ko@ucdmc.ucdavis.edu.

10Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York. Department of Surgery, Mount Sinai School of Medicine, New York, New York. shu-hsia.chen@mssm.edu eric.ko@ucdmc.ucdavis.edu.