Targeting myeloid-derived suppressor cells to attenuate vasculogenic mimicry and synergistically enhance the anti-tumor effect of PD-1 inhibitor

Yinan Li; Kailiang Qiao; Xiaoyun Zhang; Haoyang Liu; Heng Zhang; Zhiyang Li; Yanrong Liu; Tao Sun

doi:10.1016/j.isci.2021.103392

Targeting myeloid-derived suppressor cells to attenuate vasculogenic mimicry and synergistically enhance the anti-tumor effect of PD-1 inhibitor

iScience. 2021 Nov 1;24(12):103392. doi: 10.1016/j.isci.2021.103392. eCollection 2021 Dec 17.

Authors

Yinan Li^{1

2}, Kailiang Qiao^{1

2}, Xiaoyun Zhang^{1

2}, Haoyang Liu^{1

2}, Heng Zhang^{1

2}, Zhiyang Li^{1

2}, Yanrong Liu³, Tao Sun^{1

2}

Affiliations

¹ State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin 300350, China.
² Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin 300450, China.
³ Molecular Pathology Institute of Gastrointestinal Tumors, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining 272013, Shandong, China.

Abstract

Myeloid-derived suppressor cells (MDSCs) enhance the proliferation of endothelial cells to stimulate angiogenesis. However, many aggressive malignant tumors do not have endothelial cell-dependent blood vessels in the early stage and instead generate microcirculation by forming vasculogenic mimicry (VM). To date, the relationship between MDSCs and tumor cells remains the focus of ongoing studies. In this work, MDSCs were co-cultured with mouse melanoma cells and can enhance proliferation and VM formation of melanoma cells. For MDSCs targeting, doxycycline (DOX) was found to selectively suppress PMN-MDSCs but has no influence on T cells. In addition, DOX pretreatment substantially reduced the promoting ability of MDSCs for the VM formation of B16-F10 cells. DOX also inhibited tumor growth and enhanced the antitumor activity of PD-1 inhibitors in C57BL6 and BALB/c mice subcutaneously inoculated with B16-F10 and 4T1 cells, respectively. In conclusion, the combination of DOX and PD-1 inhibitor could be an anticancer strategy.

Keywords: Cancer; Genetics.