Intratumoral interleukin-9 delineates a distinct immunogenic class of gastric cancer patients with better prognosis and adjuvant chemotherapeutic response
Intratumoral interleukin-9 delineates a distinct immunogenic class of gastric cancer patients with better prognosis and adjuvant chemotherapeutic response
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DOI：
10.1080/2162402x.2020.1856468
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Zhenbin Shen
中科院分区：
文献类型：
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作者：
H Fang;Y Gu;Yuchao Fei;Kaifeng Jin;Yifan Chen;Yifan Cao;Xin Liu;Kunpeng Lv;Jieti Wang;Kuan Yu;Chao Lin;Hao Liu;He Li;Hongyong He;Weijuan Zhang;Heng Zhang;Zhenbin Shen
Interleukin-9 (IL-9) is a T cell cytokine that is associated with inflammation and allergy, but the expression level of IL-9 in gastric cancer and its clinical significance are less well established. Our study aims to uncover the critical role of IL-9 in the progression of gastric cancer. Here, a total of 453 patients with gastric cancer undergoing curative resection were enrolled for immunohistochemical analyses, and Kaplan-Meier analysis was conducted to compare overall survival of patients in different subgroups. We further investigated the correlation between IL-9 expression and functional status of intratumoral CD8+ T cells by means of Flow cytometry. Moreover, in vitro study was preformed to further explore the influence of IL-9 on anti-tumor immunity. Results indicated that gastric cancer patients with high IL-9 expression showed improved overall survival and gained more benefit from 5-fluorouracil-based adjuvant chemotherapy (ACT). High IL-9 expression was associated with increased numbers and elevated function of intratumoral CD8+ T cells. In vitro study revealed that recombinant human IL-9 (rhIL-9) exhibit anti-tumor activity via enhancing the function of intratumoral CD8+ T cells. Moreover, we found rhIL-9 could augment the efficacy of Pembrolizumab in gastric cancer. In summary, these results suggest that IL-9 expression could act as an independent predictor for overall survival and ACT response and enhancing IL-9 signaling might represent an important therapeutic strategy in gastric cancer.
