Abstract 1589: Presence of PD-L1+ tumor cells in tumor tissue and blood significantly associated with T/N stage and lymphovascular invasion in colorectal cancer patients

Abstract

Abstract Background: PD-L1 assessment on tumor tissue is considered as an important predictive marker for anti-PD-1 treatments and has been approved by FDA as companion diagnostics for immunocheckpoint antagonists. Nonetheless, it remains challenging because of the dynamic nature and heterogeneity of PD-L1 expression, and the availability of tumor tissue. Measurement of circulating tumor cells (CTC) serves a form of liquid biopsy and tumor biomarker due to its non-invasiveness and real-time assessment. Here, we analyzed and compared PD-L1 expression in CTCs and tumor cells harvested from surgical specimen from colorectal cancer (CRC) patients. Methods: Mesenteric vein blood (MVB) samples were collected into K2EDTA-containing vacationer tubes and subsequently performed CTC enumeration and PD-L1 analysis by MiSelect R system. Tumor tissues were homogenized via collagenase enzyme digestion to single cell suspension before subjected to MiSelect R analysis. Tumor cells and CTCs are defined as EpCAM+, cytokeratin+ and CD45- with intact nuclei. PD-L1 analysis was performed by anti-PD-L1 primary antibody (clone 28-8). Tumor cells, CTCs and PD-L1+ tumor cells were counted and compared among different clinicopathological parameters. Results: MVB sample were collected intraoperatively from 116 CRC patients across various stages (stage I: 24, II: 38, III:42 and IV:12). CTC presence correlated with T stage and CEA level (P = 0.018 and 0.049, respectively); furthermore, PD-L1+ CTC presence significantly correlated with clinical stage, N stage, microscopic blood vascular and lymphatic vascular invasion (P = 0.0017, 0.013, 0.014 and 0.004, respectively). The percentage of PD-L1+ tumor cells showed positive correlation between tumor tissue and CTC, and both correlated with tumor stage. Conclusion: PD-L1+ cell was detectable in both tumor tissue and CTC in CRC patients and its percentage increased as disease progressed, which might reflect escape of tumor cell from immune surveillance. The percentage of PD-L1 expression on CTCs correlated with that in paired tumor tissues. On the other hand, the expression of PD-L1 on CTC was significantly associated with blood and lymphatic vessel invasion, which might be one of the potential mechanisms for local and distant metastasis of cancer. Further investigation is warranted to better understand the clinical significances of PD-L1-expression on CTCs and its potential utility as prognostic biomarker for cancer immunotherapy. Citation Format: Ju-Yu Tseng, Chwen-Cheng Chen, Yen-Ru Chen, Chia-Ying Lee, Chun-Chi Lin, Shin-Hang Wang, Tzu-Chao Hung, Hong-Ling Wang, Yi Chung, Yen-Lun Tseng, Mu-Yi Chen, Jeng-Kai Jiang. Presence of PD-L1+ tumor cells in tumor tissue and blood significantly associated with T/N stage and lymphovascular invasion in colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1589.