Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Ann Surg Oncol. 2021 Oct;28(11):6439-6450. doi: 10.1245/s10434-021-09815-0. Epub 2021 Mar 18.
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.
We aimed to investigate the postoperative prognostic and predictive significance of basophils to survival outcomes and chemotherapeutic responsiveness in resectable gastric cancer.
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.
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.
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.
几项恶性肿瘤的研究报告中均发现嗜碱性粒细胞的聚集。在胃癌中，肿瘤浸润嗜碱性粒细胞与患者总生存和化疗反应之间的关系仍然不清楚。
我们旨在研究可切除胃癌中嗜碱性粒细胞对生存结果和化疗反应的术后预后和预测意义。
本研究共纳入了 448 例胃癌患者的两个独立患者数据集。使用免疫组织化学（IHC）染色评估嗜碱性粒细胞，并研究其与临床病理特征、生存结果以及对氟尿嘧啶为基础的辅助化疗（ACT）的反应之间的相关性。此外，还应用 IHC 来描述胃癌的免疫微环境。
在发现或验证数据集中，累积的嗜碱性粒细胞提示预后较差，多变量分析表明肿瘤浸润嗜碱性粒细胞是独立的不良预后因素。此外，肿瘤浸润嗜碱性粒细胞决定了 III 期肿瘤患者对氟尿嘧啶为基础的 ACT 的治疗反应明显较差。此外，嗜碱性粒细胞的丰度与 M2 极化巨噬细胞浸润为特征的免疫逃避微环境相关。此外，我们的研究结果表明，高嗜碱性粒细胞亚组中白细胞介素 4 的表达升高，而干扰素 γ 的表达降低。
胃癌中的肿瘤浸润嗜碱性粒细胞被确定为独立的不良预后因素，并且还预测化疗反应不良，这确定了那些需要更个体化的术后辅助治疗和更严格随访的患者。此外，嗜碱性粒细胞的浸润与免疫逃避的肿瘤微环境相关，这可能是胃癌的潜在免疫治疗靶点。
