Anti-PD-1 Therapy Response Predicted by the Combination of Exosomal PD-L1 and CD28

被引:55
作者
Zhang, Chaoxu [1 ,2 ]
Fan, Yibo [1 ,2 ]
Che, Xiaofang [1 ,2 ]
Zhang, Min [1 ,2 ]
Li, Zhi [1 ,2 ]
Li, Ce [1 ,2 ]
Wang, Shuo [1 ,2 ]
Wen, Ti [1 ,2 ]
Hou, Kezuo [1 ,2 ]
Shao, Xinye [1 ,2 ]
Liu, Yunpeng [1 ,2 ]
Qu, Xiujuan [1 ,2 ]
机构
[1] China Med Univ, Dept Med Oncol, Hosp 1, Shenyang, Peoples R China
[2] China Med Univ, Key Lab Anticancer Drugs & Biotherapy Liaoning Pr, Hosp 1, Shenyang, Peoples R China
基金
中国国家自然科学基金;
关键词
exosomal PD-L1; CD28; immune checkpoint inhibitor; response prediction; anti-PD-1; therapy; TUMOR MUTATIONAL BURDEN; LIGAND; EXPRESSION; ANTITUMOR IMMUNITY; CELL; CANCER; NIVOLUMAB; EFFICACY; PEMBROLIZUMAB; CHEMOTHERAPY; BIOMARKERS;
D O I
10.3389/fonc.2020.00760
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Anti-PD-1 therapy has been approved for cancer treatment. However, the response rate is unsatisfactory. The expression of PD-L1 in tumor tissues is unreliable to predict the treatment response. Recent studies have suggested that exosomal PD-L1 not only exerts immunosuppressive effects but also plays a significant role in the development of tumor microenvironment. Thus, the present study aims to investigate exosomal PD-L1 in improving its predictive value and efficacy. A total of 44 patients of advanced tumors of several types, treated with anti-PD-1 therapy, were enrolled. Exosomes were collected and purified from plasma. The exosomal PD-L1 was detected with ELISA. The cytokines were measured with the MILLIPLEX magnetic bead assay. Compared to the responders, exosomal PD-L1 of the non-responders was significantly higher than that of the responders (P= 0.010) before the treatment. Concurrently, exosomal PD-L1 and tumor burden decreased when the therapy was effective. And, the baseline expression of CD28 was higher in the responders than that in the non-responders (P= 0.005). Univariate and multivariate analyses validated with 1,000 times bootstrapping suggested that high exosomal PD-L1 and low CD28 expressions were negative factors for progression-free survival (PFS) of the patients who underwent anti-PD-1 treatment. The combination of exosomal PD-L1 and CD28 obtained more area under the curve (AUC) of receiver operating characteristic (ROC) (AUC 0.850 vs. 0.784 vs. 0.678) and showed a higher probability of no progression via nomograph. These findings suggested that the expression of exosomal PD-L1 and CD28 could serve as the predictive biomarkers for clinical responses to anti-PD-1 treatment.
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页数:16
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