Xu Yun, Chen Lujun, Xu Bin, Xiong Yuqi, Yang Min, Rui Xiaohui, Shi Liangrong, Wu Changping, Jiang Jingting, Lu Binfeng
Cell Physiol Biochem. 2017;41(2):475-483. doi: 10.1159/000456600. Epub 2017 Jan 30.
BACKGROUND/AIMS: T-bet, a member of the T-box family of transcription factors, is a key marker of type I immune response within the tumor microenvironment, and has been previously reported by us to serve as an important prognostic indicator for human gastric cancer patients and a potential biomarker for immunotherapy. In the present study, we aimed to assess the clinical significance and prognostic value of T-bet+ tumor-infiltrating lymphocytes in human epithelial ovarian cancer.
The immunohistochemistry was used to analyze the infiltration density of T-bet+ lymphoid cells in human epithelial ovarian cancer tissues, and the flow cytometry analysis was used to further analyze the presence of T-bet+ tumor-infiltrating lymphocytes subgroups in cancer tissues.
Our immunohistochemistry analysis showed increased number of T-bet+ lymphoid cells in the human epithelial ovarian cancer tissues, and the flow cytometry analysis further demonstrated the presence of T-bet+ tumor-infiltrating lymphocytes subgroups including CD4+ , CD8+ T cells and NK cells. In addition, we also observed a significant association of T-bet+ tumor-infiltrating lymphocytes density in the tumor nest of cancer with not only serum CA125 levels but also with distant metastasis. However no association was observed with other characteristics like patients' age, pathological type, FIGO stage, tumor site and tumor size. Furthermore, the survival analysis showed that higher density of T-bet+ tumor-infiltrating lymphocytes both in tumor nest and tumor stroma of cancer tissues was significantly associated with better patient survival. In addition, the density of T-bet+ tumor-infiltrating lymphocytes in tumor nest appeared to be an independent risk factor for predicting patients' postoperative prognoses.
Our data indicated that the key transcription factor T-bet might play an important role in the type I immune cells mediated antitumor response, and the density of T-bet+ lymphocytes in human epithelial ovarian cancer tissues could serve as a prognostic predictor for ovarian cancer patients.
背景/目的：T-bet是T-box转录因子家族的成员，是肿瘤微环境中I型免疫反应的关键标志物，我们之前曾报道其可作为人类胃癌患者的重要预后指标和免疫治疗的潜在生物标志物。在本研究中，我们旨在评估T-bet阳性肿瘤浸润淋巴细胞在人上皮性卵巢癌中的临床意义和预后价值。
采用免疫组织化学分析人上皮性卵巢癌组织中T-bet阳性淋巴细胞的浸润密度，采用流式细胞术分析癌组织中T-bet阳性肿瘤浸润淋巴细胞亚群的存在情况。
我们的免疫组织化学分析显示人上皮性卵巢癌组织中T-bet阳性淋巴细胞数量增加，流式细胞术分析进一步证实存在包括CD4+、CD8+T细胞和NK细胞在内的T-bet阳性肿瘤浸润淋巴细胞亚群。此外，我们还观察到癌组织肿瘤巢中T-bet阳性肿瘤浸润淋巴细胞密度不仅与血清CA125水平显著相关，还与远处转移显著相关。然而，未观察到与患者年龄、病理类型、国际妇产科联盟（FIGO）分期、肿瘤部位和肿瘤大小等其他特征的相关性。此外，生存分析表明，癌组织肿瘤巢和肿瘤基质中T-bet阳性肿瘤浸润淋巴细胞密度较高与患者更好的生存显著相关。此外，肿瘤巢中T-bet阳性肿瘤浸润淋巴细胞密度似乎是预测患者术后预后的独立危险因素。
我们的数据表明，关键转录因子T-bet可能在I型免疫细胞介导的抗肿瘤反应中发挥重要作用，人上皮性卵巢癌组织中T-bet阳性淋巴细胞密度可作为卵巢癌患者的预后预测指标。
