Abstract 5540: Clinical significance of soluble forms of immune checkpoint molecules in advanced esophageal cancer
Authors: Yoshida Juichiro , Ishikawa Takeshi , Ohta Takayuki , Yasuda Tomoyo , Dohi Osamu , Okayama Tetsuya , Yoshida Naohisa , Kamada Kazuhiro , Uchiyama Kazuhiko , Handa Osamu , Takagi Tomohisa , Konishi Hideyuki , Naitoh Yuji , Itoh Yoshito 
Published: August 2018

Abstract
Background: Immune checkpoint molecules such as PDL1 and CD155 are expressed on cancer cells and regulate tumor immunity by binding to ligands on immune cells. Although soluble forms of immune checkpoint molecules have been detected in the blood, the roles of these soluble forms have not been fully elucidated. In this study, the clinical significance of soluble forms of immune checkpoint molecules in advanced esophageal cancer was examined. Methods: Soluble PDL1 (sPDL1), PD1(sPD1), CD155(sCD155), and LAG3 (sLAG3) were measured by ELISA in 47 patients who were diagnosed with advanced esophageal cancer and planned to receive multidisciplinary treatment in our department from April 2015 to March 2017. The levels of these molecules in cancer patients were compared with those of 24 control subjects. Results: The mean age of the tumor group was 66 years (41 years to 78 years), the ratio of males and females was 42: 5. Based on TNM-UICC stage grouping, 8, 24 and 15 patients were in clinical stage II, III and IV, respectively. All patients underwent chemotherapy, 25 patients underwent radiation therapy in combination with chemotherapy, and 26 underwent surgical therapy after chemotherapy. There was no difference in age between two groups, but the proportion of male was significantly higher in the cancer group than in the tumor group (P = 0.014). Regarding sPDL1 and sLAG3, there was no significant difference between two groups, but the levels of sPD1 and sCD155 were significantly higher in the tumor group than the control group (sPD1: P = 0.0225; sCD155: P = 0.0006). In subgroup analysis of patients with esophageal cancer, there was a tendency for higher levels of sPD1 in patients with lymph node metastasis (P = 0.150), large tumor diameter (P = 0.189), and higher levels of serum SCC (P = 0.078). The level of sPD1 was related to neither response rate nor overall survival. On the other hand, we did not find any association between clinical characteristics and the level of sCD155. However, the level of sCD155 tended to be higher in patients with response to chemotherapy (CR / PR) (P = 0.111) and in patients with a longer survival (P = 0.183). Discussion: We confirmed that sPD1 and sCD155 are elevated in advanced esophageal cancer. In addition, results in this study suggested that sCD155 may be a biomarker for therapeutic effect or prognostic prediction of esophageal cancer. Large-scale studies are needed to confirm our findings.
Citation Format: Juichiro Yoshida, Takeshi Ishikawa, Takayuki Ohta, Tomoyo Yasuda, Osamu Dohi, Tetsuya Okayama, Naohisa Yoshida, Kazuhiro Kamada, Kazuhiko Uchiyama, Osamu Handa, Tomohisa Takagi, Hideyuki Konishi, Yuji Naitoh, Yoshito Itoh. Clinical significance of soluble forms of immune checkpoint molecules in advanced esophageal cancer [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 5540.