化学免疫疗法
医学
卵巢癌
紫杉醇
癌症研究
肿瘤微环境
封锁
免疫疗法
癌症
肿瘤科
内科学
免疫学
受体
作者
Mingyan Huang,Jianhua Luo,Xinpei Ji,Miao Hu,Yiquan Xue,Qiuyan Liu
标识
DOI:10.1016/j.phrs.2022.106512
摘要
As a high mortality gynecological malignancy, most ovarian cancer patients experience refractory to standard chemotherapy, current immunotherapy or chemoimmunotherapy in clinic and clinical trials. The underlying mechanisms and biomarkers predictive of response for patient selection is quite urgent. In this study, we found that the level of tumor-expressed B7-H3 is positively correlated with the poorer prognosis in ovarian cancer patients. Therapeutically, in syngeneic mouse model of ovarian cancer, deficiency of tumor-expressed B7-H3 significantly potentiates the anti-tumor efficacy of paclitaxel or PD-L1 blockade monotherapy. However, combination of paclitaxel plus anti-PD-L1 has no synergistic effects than PD-L1 blockade monotherapy. Mechanistically, deficiency of tumor-expressed B7-H3 attenuates inflammatory cytokine IL-6 production, upregulates type I interferon (IFN) expression and increases paclitaxel-induced tumor cells apoptosis via caspase 3 activation pathway, resulting in reprogramming the tumor microenvironment including increasing the infiltration of effector T lymphocytes and decreasing the recruitment of Ly6G+CD11b+ myeloid-derived suppressor cells (MDSCs) in vivo. Collectively, these results demonstrate that deficiency of tumor-expressed B7-H3 enhances the anti-tumor efficacy of paclitaxel or PD-L1 blockade monotherapy rather than their combined chemoimmunotherapy in ovarian cancer, suggesting that B7-H3 may be a potential predictive biomarker for beneficial patient stratification and a candidate therapeutic target in ovarian cancer.
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