Intratumoral interleukin-9 delineates a distinct immunogenic class of gastric cancer patients with better prognosis and adjuvant chemotherapeutic response.
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| Abstract |
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.
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| Authors | H Fang, R Li, 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 |
| Journal | Oncoimmunology (Oncoimmunology) Vol. 9 Issue 1 Pg. 1856468 (12 15 2020) ISSN: 2162-402X [Electronic] United States |
| PMID | 33354409 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC. |
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