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

Frontiers in Oncology

Xiaofang Che²  Yibo Fan²  Min Zhang²  Ce Li²  Yunpeng Liu²  Chaoxu Zhang²  Kezuo Hou²  Xiujuan Qu²  Shuo Wang²  Ti Wen²  Zhi Li²  Xinye Shao² 

[1] Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China;Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China;

关键词: exosomal PD-L1;    CD28;    immune checkpoint inhibitor;    response prediction;    anti-PD-1 therapy;   

DOI  :  10.3389/fonc.2020.00760

来源: DOAJ

【 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.

【 授权许可】

Unknown