1. Enhanced tumor response to radiotherapy after PD-1 blockade in metastatic gastric cancer
- Author
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Saori Mishima, Hirofumi Kuno, Daisuke Kotani, Hidehiro Hojo, Kentaro Sawada, Shun-ichiro Kageyama, Takayuki Yoshino, Akihito Kawazoe, Yosuke Togashi, Kenji Takashima, Kohei Shitara, Tomohiro Kadota, Yasutoshi Kuboki, Yoshiaki Nakamura, Tomonori Yano, Hiroya Taniguchi, Tetsuo Akimoto, Yusuke Yoda, Toshihiko Doi, Takashi Kojima, Naoki Nakamura, Hiroyoshi Nishikawa, Akinori Sasaki, and Tatsushi Kobayashi
- Subjects
Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Regulatory T cell ,medicine.medical_treatment ,T cell ,Programmed Cell Death 1 Receptor ,Adenocarcinoma ,CD8-Positive T-Lymphocytes ,Radiation Tolerance ,T-Lymphocytes, Regulatory ,03 medical and health sciences ,Lymphocytes, Tumor-Infiltrating ,0302 clinical medicine ,Stomach Neoplasms ,Surgical oncology ,Internal medicine ,Tumor Microenvironment ,medicine ,Humans ,Immune Checkpoint Inhibitors ,Aged ,Retrospective Studies ,Tumor microenvironment ,Radiotherapy ,Tumor-infiltrating lymphocytes ,business.industry ,Gastroenterology ,General Medicine ,Prognosis ,medicine.disease ,Primary tumor ,Radiation therapy ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,030211 gastroenterology & hepatology ,business ,CD8 ,Follow-Up Studies - Abstract
Immune checkpoint inhibitors may enhance the efficacy of radiotherapy (RT) in cancer treatment but the effect remains unknown in metastatic gastric cancer (mGC). This study aimed to compare the tumor shrinkage by palliative RT for mGC patients with or without previous exposure to anti-PD-1 therapy. Data of 36 mGC patients who had received palliative RT from April 2013 to May 2019 were analyzed. Primary tumor responses were evaluated through a volumetric measurement-based method using computed tomography (CT) and endoscopic responses were evaluated in patients who underwent endoscopy before and after RT. Tumor microenvironment (TME) immune status was investigated by analyzing tumor-infiltrating lymphocytes by flow cytometry. Among 36 patients, 18 had previous exposure to anti-PD-1 before RT showing no significant differences in baseline characteristics with the other 18 patients without exposure to anti-PD-1 treatment. Tumor responses were observed in 28% (5/18) and none (0/18) in the anti-PD-1-exposed vs. naive group, respectively (P = 0.045). Five out of eight patients in the anti-PD-1-exposed group, who underwent endoscopy after RT showed partial response, but none in the anti-PD-1-naive patients showed response (P = 0.026). Increase in the CD8+ T cell/effector regulatory T cell ratio in TILs after anti-PD-1 therapy was noted in three responders to RT, but not in the other three non-responders. Prior exposure to anti-PD-1 therapy increases tumor response to RT. Immune profiling suggests that anti-PD-1 therapy may enhance the efficacy of RT by immunoactivation in the TME.
- Published
- 2020
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