Dynamic change of PD-L1 expression on circulating tumor cells in advanced solid tumor patients undergoing PD-1 blockade therapy

Chunyan Yue; Yubo Jiang; Ping Li; Yuehua Wang; Jian Xue; Nannan Li; Da Li; Ruina Wang; Yongjun Dang; Zhiyuan Hu; Yanlian Yang; Jianming Xu

doi:10.1080/2162402X.2018.1438111

Dynamic change of PD-L1 expression on circulating tumor cells in advanced solid tumor patients undergoing PD-1 blockade therapy

Oncoimmunology. 2018 Mar 6;7(7):e1438111. doi: 10.1080/2162402X.2018.1438111. eCollection 2018.

Authors

Chunyan Yue^{1

2}, Yubo Jiang³, Ping Li¹, Yuehua Wang¹, Jian Xue⁴, Nannan Li⁴, Da Li⁴, Ruina Wang^{5

6}, Yongjun Dang^{5

6}, Zhiyuan Hu^{1

2

7}, Yanlian Yang^{1

2}, Jianming Xu³

Affiliations

¹ CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory for Biomedical Effects of Nanomaterial and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, P. R. China.
² Sino-Danish College, University of Chinese Academy of Sciences, Beijing, P. R. China.
³ Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, P. R. China.
⁴ Nanopep Biotech Co., Beijing, P. R. China.
⁵ Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai China.
⁶ Department of Pulmonary and Critical Care Medicine, Huashan Hospital, Fudan University, Shanghai, China.
⁷ Center for Neuroscience Research, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian Province, P. R. China.

Abstract

Background: Tumor PD-L1 levels have predictive value in PD-1/PD-L1 checkpoint blockade therapies, yet biopsies can only provide baseline information. Whether PD-L1 expression on circulating tumor cells (CTCs) could serve as an alternative biomarker is of great interest. Design: We established an immunofluorescence assay for semi-quantitative assessment of the PD-L1 expression levels on CTCs with four categories (PD-L1^negative, PD-L1^low, PD-L1^medium and PD-L1^high). 35 patients with different advanced gastrointestinal tumors were enrolled in a phase 1 trial of a PD-1 inhibitor, IBI308. The CTC numeration and the PD-L1 expression levels were analyzed. Results: Prior the treatment of IBI308, 97% (34/35) patients had CTCs, ranging from1 to 70 (median 7). 74% (26/35) had PD-L1^positive CTCs, and 60% (21/35) had at least one PD-L1^high CTCs. The disease control (DC) rate in PD-L1^high patients (48%) is much higher than the others (14%). The group with at least 20% abundance of PD-L1^high CTCs had even higher DC rate of 64% (9/14), with only 14% DC rate for the rest (3/21). We also observed that the count changes of total CTC, PD-L1^postive CTC and PD-L1^high CTC correlate quite well with disease outcome (P<0.001, P = 0.002 and 0.007, respectively). In addition, the abundance of PD-L1^high CTCs at baseline had predicative significance for progression free survival (PFS). Conclusions: We revealed that the abundance of PD-L1^high CTCs at baseline might serve as a predictor to screen patients for PD-1/PD-L1 blockade therapies and measuring the dynamic changes of CTC could indicate the therapeutic response at early time.

Keywords: advanced solid tumor; circulating tumor cells (CTCs); immunotherapy; programmed death-ligand 1 (PD-L1); semi-quantitative analysis.

Publication types

Research Support, Non-U.S. Gov't

Grants and funding

Key Research Program of the Chinese Academy of Sciences (No. KFZD-SW-210), Beijing Municipal Science and Technology Project (No.Z171100002017013), “Strategic Priority Research Program” of Chinese Academy of Sciences (XDA09040300), National Natural Science Foundation of China (No. 21775031, 81500900 & 21503054), Beijing Talents Fund (No. 2015000021223ZK36), Beijing Municipal Natural Science Foundation (No. L172035 & 2172056).