Enhanced tumor response to radiotherapy after PD-1 blockade in metastatic gastric cancer

Akinori Sasaki, Yoshiaki Nakamura, Yosuke Togashi, Hirofumi Kuno, Hidehiro Hojo, Shunichiro Kageyama, Naoki Nakamura, Kenji Takashima, Tomohiro Kadota, Yusuke Yoda, Saori Mishima, Kentaro Sawada, Daisuke Kotani, Akihito Kawazoe, Yasutoshi Kuboki, Hiroya Taniguchi, Takashi Kojima, Toshihiko Doi, Takayuki Yoshino, Tomonori YanoTatsushi Kobayashi, Tetsuo Akimoto, Hiroyoshi Nishikawa, Kohei Shitara

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


Background: 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. Methods: 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. Results: 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. naïve 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-naïve 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. Conclusions: 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.

Original languageEnglish
Pages (from-to)893-903
Number of pages11
JournalGastric Cancer
Issue number5
Publication statusPublished - Sept 1 2020
Externally publishedYes


  • Anti-PD-1 therapy
  • Immune checkpoint inhibitors
  • Radiotherapy
  • Tumor-infiltrating lymphocytes

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology
  • Cancer Research


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