Abstract 401: Clinical impact of viable circulating tumor cells (v-CTC) detection and PD-L1 expression on v-CTC in the patients with resectable pancreatic cancer
Authors: Masahiro Tanemura, Kenta Furukawa, Manabu Mikamori, Takurou Saito, Masahisa Otsuka, Yozo Suzuki, Kentaro Kishi, Hironao Yasuoka, Masahiko Tsujimoto, Yasuo Urata, Hiroki Akamatsu
Journal: Cancer Research (2019)

Abstract [Introduction] The capture and analysis of CTCs as “liquid biopsy” provides the possibility to avoid invasive biopsies, obvious implications in cancer diagnosis and staging. We tested novel methods for viable CTCs (v-CTC) isolation in the patients (pts) with pancreatic cancer (PC), and investigated the clinical potential of v-CTCs in prognosis. We analyzed the PD-L1(L1) expression in both PC tumors and v-CTCs. [Pts and Methods] 7.5 ml of venous blood was collected prospectively from 39 PC pts, either surgery first (S group) or pre-treatment, consisted of Gem:800mg/m2; and S-1:80mg/m2 given concurrently with IMRT to 60Gy (NACRT:N group). To detect v-CTCs, we employed a telomerase-specific replication-selective adenovirous expressing GFP. For S group, samples were obtained before/after resection. For N group, samples were obtained before/after NACRT and after resection. To distinguish between leucocyte and cells with either epithelial or mesenchymal origin, cells were stained by anti-CD45, anti-Cytokeratin and anti-Vimentin Abs. GFP-positive and CD45-negative cells were counted as v-CTC. To assess L1 expression in PC tissues (IHC) and v-CTCs, L1 IHC kit (22C3, for tissues) and anti-human L1 mAb(MIH1,for CTCs) were employed. [Results]S group: 24 pts aged 53~85 years (male/female=12/12) were enrolled. 24 pts underwent curative resection. No v-CTCs were detected in 6 pts at both before and after resection, and 5 of 6 pts survived without recurrence. V-CTCs were identified in 18 of 24 pts, and 13 of 18 pts developed liver metastasis. Marked decrease of CTC counts were seen after resection in 10 of 18 pts, but 9 pts developed recurrence. N group: 15 PC pts aged 44~77 years (male/female=4/11) were enrolled. 15 pts underwent curative resection. No v-CTCs were detected in 5 pts, and 5 pts survived without recurrence. V-CTCs was identified in 10 of 15 pts, and only 3 out of 10 pts developed disease recurrence. Marked increase in CTC counts was observed after NACRT in 5 of 6 CTC-positive pts before NACRT, and 3 of 5 pts developed liver metastasis and died. NACRT may induce tumor cell dissemination into the blood circulation for CTC-positive pts. PD-L1 expression: L1 expression were assessed for 21 pts (S group:18, N group: 3). No patients with IHC-L1 high expression (≥50%) were observed (&amp;lt;1% [negative]:9, 10%:6, 20%:4, 40%:2). For S group, IHC-L1 low +/CTC-L1 + were detected in 12/18 pts (66%). IHC-L1-/CTC-L1+ were detected in 3/18 pts (17%). IHC-L1 - /no detectable CTCs were detected in 3/18 pts (17%). For N group, IHC-L1 - were detected in 3 pts, but CTCs-L1 + were detected in 2 pts (1 pt had no CTCs). The majority of detectable v-CTCs were positive for L1-expression (89% [92/103 CTCs]), despite L1-negative or -low expression in PC tissues. [Conclusions] Viable CTC detection appears as a promising prognostic marker. Immunotherapy with anti-PD-1/PD-L1 Abs may effectively target v-CTCs. Note: This abstract was not presented at the meeting. Citation Format: Masahiro Tanemura, Kenta Furukawa, Manabu Mikamori, Takurou Saito, Masahisa Otsuka, Yozo Suzuki, Kentaro Kishi, Hironao Yasuoka, Masahiko Tsujimoto, Yasuo Urata, Hiroki Akamatsu. Clinical impact of viable circulating tumor cells (v-CTC) detection and PD-L1 expression on v-CTC in the patients with resectable pancreatic cancer [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 401.