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Clinical significance of soluble forms of immune checkpoint molecules in advanced esophageal cancer

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Abstract

Immune checkpoint molecules 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 of patients with some types of tumors, their roles have not been fully elucidated. Soluble PD-L1, PD-1, CD155, LAG3, and CD226 (sPD-L1, sPD-1, sCD155, sLAG3, and sCD226, respectively) were measured in the sera of 47 patients with advanced esophageal cancer and compared with those of 24 control subjects. Pretreatment levels of sPD-1 and sCD155 were significantly higher in the patients with cancer than in the control subjects (P = 0.023, P = 0.001). The sPD-1 levels tended to be higher in the patients with lymph node metastasis, a large tumor diameter, and higher levels of serum SCC antigen (P = 0.150, P = 0.189, and P = 0.078, respectively). However, higher levels of sCD155 were associated with a better response to chemotherapy and favorable overall survival (P = 0.111 and P = 0.068, respectively). After 2 courses of chemotherapy, the levels of sCD155 and sCD226 were significantly increased (P < 0.001 and P = 0.002, respectively). Moreover, the increase in sCD226 during chemotherapy was associated with poor treatment response (P = 0.019). sPD-1 levels are possibly dependent on the tumor aggressiveness of the esophageal cancer. Furthermore, the pretreatment levels of sCD155 and kinetic change of sCD226 after chemotherapy may be used as biomarkers of the treatment response and prognosis in patients with esophageal cancer.

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Acknowledgements

This work was supported by the Kurozumi Medical Foundation and Grant-in-Aid for Scientific Research (KAKENHI C) (17K09314) from the Japan Society for the Promotion of Science (JSPS).

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  1. Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto, 602-8566, Japan

    Juichiro Yoshida, Takeshi Ishikawa, Toshifumi Doi, Takayuki Ota, Tomoyo Yasuda, Tetsuya Okayama, Naoyuki Sakamoto, Ken Inoue, Osamu Dohi, Naohisa Yoshida, Kazuhiro Kamada, Kazuhiko Uchiyama, Tomohisa Takagi, Hideyuki Konishi, Yuji Naito & Yoshito Itoh

  2. Outpatient Oncology Unit, University Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Takeshi Ishikawa

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Correspondence to Takeshi Ishikawa.

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This study was performed with the approval of the Ethics Review Boards of Kyoto Prefectural University of Medicine (Approval No. ERB-C-150-1).

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Yoshida, J., Ishikawa, T., Doi, T. et al. Clinical significance of soluble forms of immune checkpoint molecules in advanced esophageal cancer. Med Oncol 36, 60 (2019). https://doi.org/10.1007/s12032-019-1285-x

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