Xudong He1, Yifan Cao2, Yun Gu1, Hanji Fang1, Jieti Wang3, Xin Liu1, Kunpeng Lv1, Kuan Yu2, Yuchao Fei1, Chao Lin2, Hao Liu2, Heng Zhang2, He Li2, Jiejie Xu1, Ruochen Li4, Hongyong He5. 1. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China. 2. Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. 3. Department of Gastric Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China. 4. Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. rcli12@fudan.edu.cn. 5. Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. he.hongyong@zs-hospital.sh.cn.
Abstract
BACKGROUND: Accumulation of basophils has been reported in several malignancies. In gastric cancer, the relation between tumor-infiltrating basophils and patient overall survival and chemotherapeutic responsiveness still remains obscure. OBJECTIVE: We aimed to investigate the postoperative prognostic and predictive significance of basophils to survival outcomes and chemotherapeutic responsiveness in resectable gastric cancer. METHODS: The study enrolled two independent patient data sets with 448 gastric cancer patients overall. Basophils were evaluated with the use of immunohistochemistry (IHC) staining, and the correlation with clinicopathological characteristics, survival outcomes, and responsiveness to fluorouracil-based adjuvant chemotherapy (ACT) were investigated. Additionally, IHC was applied to characterize immune contexture in gastric cancer. RESULTS: In either the discovery or validation data sets, accumulated basophils indicated poorer prognosis, and tumor-infiltrating basophils were identified as an independent adverse prognostic factor by multivariate analysis. Furthermore, tumor-infiltrating basophils determined significantly inferior therapeutic responsiveness to fluorouracil-based ACT in patients with stage III tumors. In addition, the abundance of basophils was correlated with an immunoevasive contexture characterized by M2-polarized macrophage infiltration. Moreover, our findings indicated elevated interleukin-4 expression but decreased interferon-γ expression in the high-basophils subgroup. CONCLUSIONS: Tumor-infiltrating basophils in gastric cancer were identified as an independent adverse prognosticator, and also predicted inferior chemotherapeutic responsiveness, which identified those patients in need of much more individualized postoperative adjuvant therapy and more stringent follow-up. Furthermore, the infiltration of basophils was associated with immunoevasive tumor microenvironment, which might be a potential immunotherapeutic target for gastric cancer.
BACKGROUND: Accumulation of basophils has been reported in several malignancies. In gastric cancer, the relation between tumor-infiltrating basophils and patient overall survival and chemotherapeutic responsiveness still remains obscure. OBJECTIVE: We aimed to investigate the postoperative prognostic and predictive significance of basophils to survival outcomes and chemotherapeutic responsiveness in resectable gastric cancer. METHODS: The study enrolled two independent patient data sets with 448 gastric cancerpatients overall. Basophils were evaluated with the use of immunohistochemistry (IHC) staining, and the correlation with clinicopathological characteristics, survival outcomes, and responsiveness to fluorouracil-based adjuvant chemotherapy (ACT) were investigated. Additionally, IHC was applied to characterize immune contexture in gastric cancer. RESULTS: In either the discovery or validation data sets, accumulated basophils indicated poorer prognosis, and tumor-infiltrating basophils were identified as an independent adverse prognostic factor by multivariate analysis. Furthermore, tumor-infiltrating basophils determined significantly inferior therapeutic responsiveness to fluorouracil-based ACT in patients with stage III tumors. In addition, the abundance of basophils was correlated with an immunoevasive contexture characterized by M2-polarized macrophage infiltration. Moreover, our findings indicated elevated interleukin-4 expression but decreased interferon-γ expression in the high-basophils subgroup. CONCLUSIONS:Tumor-infiltrating basophils in gastric cancer were identified as an independent adverse prognosticator, and also predicted inferior chemotherapeutic responsiveness, which identified those patients in need of much more individualized postoperative adjuvant therapy and more stringent follow-up. Furthermore, the infiltration of basophils was associated with immunoevasive tumor microenvironment, which might be a potential immunotherapeutic target for gastric cancer.
Authors: Andrea Denzel; Ulrich A Maus; Manuel Rodriguez Gomez; Cordula Moll; Marianne Niedermeier; Christine Winter; Regina Maus; Susan Hollingshead; David E Briles; Leoni A Kunz-Schughart; Yvonne Talke; Matthias Mack Journal: Nat Immunol Date: 2008-05-30 Impact factor: 25.606
Authors: Caspar Ohnmacht; Christian Schwartz; Marc Panzer; Isabell Schiedewitz; Ronald Naumann; David Voehringer Journal: Immunity Date: 2010-09-24 Impact factor: 31.745
Authors: Lindsey A Torre; Freddie Bray; Rebecca L Siegel; Jacques Ferlay; Joannie Lortet-Tieulent; Ahmedin Jemal Journal: CA Cancer J Clin Date: 2015-02-04 Impact factor: 508.702