Abstract 2218: Exosomal PD-L1 and T lymphocyte status predict the effect of anti-PD-1 therapy

Abstract

Abstract Background: Anti-PD-1 therapy is approved to be remarkable for cancer treatment. However, the response rate is dissatisfactory. PD-L1 expression in tumor tissue, which affected by chemotherapy, radiotherapy and activity of signal transduction pathways, is unreliable to predict treatment response. Recent studies suggest that exosomal PD-L1 not only exerts immunosuppressive effects besides tumors, but also plays a significant role in development of tumor microenvironment in the distance. A deeper research of exosomal PD-L1 assessment is needed to improve the predictive value and treatment efficacy. Method: We enrolled 28 patients with advanced tumor, including 8 lung adenocarcinoma, 7 lung squamous carcinoma, 4 esophageal carcinoma, 2 colorectal carcinoma, 2 cholangiocarcinoma, 1 small cell lung cancer, 1 gastric carcinoma, 1 duodenal adenocarcinoma, 1 nasopharyngeal carcinoma and 1 tongue squamous cell carcinoma, who were treated by anti-PD-1 therapy followed the standard regimens. Exosomes were collected and purified from plasma with exosome isolation kit. Exsomal PD-L1 was detected by ELISA. Peripheral blood mononuclear cells (PBMCs) were isolated using Ficoll gradient. Exhausted T lymphocyte were stained for cytometry. Result: Compared with responder, exosomal PD-L1 of non-responders is significantly higher than responder (P=0.036) before treatment. Moreover, the CD4+ and CD8+ T lymphocyte count is higher and the percentage of exhausted T lymphocyte rate is lower in responder than the non-responder cohort before treatment. Although there is no statistical difference, the level of exosomal PD-L1 decreased in responder cohortat on 6 to 8 weeks after treatment, on the contrary, increased in non-responder cohort after anti-PD-1 therapy. Concurrently, exosomal PD-L1 and tumor burden were decreased when the therapy was effective. Conclusion: Low levels of exosomal PD-L1 and exhausted T lymphocyte rate on baseline and decreasing expression of exosomal PD-L1 after treatment could screen out the potential benefit populations of anti-PD-1 therapy in a variety of solid tumors. These findings suggest that expression of exosomal PD-L1 and exhausted T lymphocyte cell rate could be attractive and predictive biomarkers for clinical responses to anti-PD-1 treatment. Note: This abstract was not presented at the meeting. Citation Format: Xiujuan Qu, Chaoxu Zhang, Yibo Fan, Xiaofang Che, Yunpeng Liu. Exosomal PD-L1 and T lymphocyte status predict the effect of anti-PD-1 therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2218.