Enhanced tumor response to radiotherapy after PD-1 blockade in metastatic gastric cancer
Enhanced tumor response to radiotherapy after PD-1 blockade in metastatic gastric cancer
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DOI：
10.1007/s10120-020-01058-4
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发表时间：
2020-03-16
期刊：
影响因子：
7.4
通讯作者：
Shitara, Kohei
中科院分区：
文献类型：
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作者：
Sasaki, Akinori;Nakamura, Yoshiaki;Shitara, Kohei
免疫检查点抑制剂可能会提高放疗（RT）在癌症治疗中的疗效，但在转移性胃癌（mGC）中的作用尚不清楚。本研究旨在比较既往接受或未接受抗pd -1治疗的mGC患者通过姑息性RT治疗的肿瘤缩小情况。方法分析2013年4月至2019年5月36例接受姑息性放疗的mGC患者的资料。通过基于体积测量的计算机断层扫描（CT）方法评估原发肿瘤反应，并评估在rt前后接受内窥镜检查的患者的内窥镜反应。通过流式细胞术分析肿瘤浸润淋巴细胞来研究肿瘤微环境（TME）免疫状态。结果在36例患者中，18例患者在接受放射治疗前曾接受过抗pd -1治疗，与其他18例未接受抗pd -1治疗的患者相比，基线特征无显著差异。抗pd -1暴露组肿瘤应答率为28%(5/18)，未见应答率为0/18 （P = 0.045）。抗pd -1暴露组8例患者中有5例在RT后进行内窥镜检查时出现部分缓解，而抗pd -1初治组没有出现缓解（P = 0.026）。在抗pd -1治疗后，3名对RT有反应的患者发现TILs中CD8(+) T细胞/效应调节性T细胞比例增加，而在其他3名无反应的患者中则没有。结论先前暴露于抗pd -1治疗可增加肿瘤对RT的反应。免疫分析提示抗pd -1治疗可能通过免疫激活TME来增强RT的疗效。
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. 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. 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.