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Helper T cell-dominant tertiary lymphoid structures are associated with disease relapse of advanced colorectal cancer.
OncoImmunology ( IF 7.2 ) Pub Date : 2020-02-17 , DOI: 10.1080/2162402x.2020.1724763
Kyoko Yamaguchi 1 , Mamoru Ito 1 , Hirofumi Ohmura 1 , Fumiyasu Hanamura 1 , Michitaka Nakano 1 , Kenji Tsuchihashi 1 , Shuntaro Nagai 2 , Hiroshi Ariyama 1 , Hitoshi Kusaba 1 , Hidetaka Yamamoto 3 , Yoshinao Oda 3 , Masafumi Nakamura 2 , Koichi Akashi 1 , Eishi Baba 4
Affiliation  

Tertiary lymphoid structures (TLSs), clusters of immune cells found around tumor tissue, have been shown to be associated with anti-tumor immunity, but the cellular composition within each TLS and whether the cellular composition of a TLS affects a patient's prognosis are poorly understood. In the present study, each TLS was categorized according to its cellular composition determined by a system of multiplex immunohistochemical staining and quantitative analysis, and the correlation between the category and prognosis was examined. Sixty-seven patients with curatively resected stage II/III colorectal cancer (CRC) were enrolled. A TLS, consisting of germinal center B cells, follicular dendritic cells, T helper (Th) cells, B cells, cytotoxic T cells, and macrophages, was confirmed in the tumor tissue of 58 patients (87%). The densities of Th cells and macrophages were significantly higher in relapsed patients than in not-relapsed patients (p = .043 and p = .0076). A higher ratio of Th cells was the most significant independent risk factor for disease relapse on multivariate analysis. The subset increasing in Th cells was GATA3+ Th2. A total of 353 TLSs was divided into five clusters according to immune cell composition. Among them, the Th-rich type TLS was significantly increased (p = .0009) in relapsed patients. These data suggest the possibility that Th cell-dominant composition might disturb the anti-tumor immune response, and the function of each TLS might differ depending on its composition.

中文翻译:

辅助性T细胞为主的三级淋巴结构与晚期大肠癌的疾病复发相关。

三级淋巴样结构(TLS)是肿瘤组织周围发现的免疫细胞簇,已被证明与抗肿瘤免疫力相关,但人们对每个TLS中的细胞组成以及TLS的细胞组成是否影响患者的预后知之甚少。在本研究中,根据TLS的细胞组成,通过多重免疫组织化学染色和定量分析系统对每个TLS进行分类,并检查其类别与预后之间的相关性。入选了67例经根治性切除的II / III期大肠癌(CRC)患者。在58例患者的肿瘤组织中证实了由生发中心B细胞,滤泡树突状细胞,T辅助(Th)细胞,B细胞,细胞毒性T细胞和巨噬细胞组成的TLS。复发患者中Th细胞和巨噬细胞的密度显着高于未复发患者(p = .043和p = .0076)。多因素分析显示,较高的Th细胞比例是疾病复发的最重要独立风险因素。Th细胞中增加的亚群是GATA3 + Th2。根据免疫细胞组成,将总共353个TLS分为五个簇。其中,富Th型TLS在复发患者中显着增加(p = .0009)。这些数据表明,Th细胞占主导地位的成分可能会干扰抗肿瘤免疫反应,每种TLS的功能可能取决于其成分而有所不同。多因素分析显示,较高的Th细胞比例是疾病复发的最重要独立风险因素。Th细胞中增加的亚群是GATA3 + Th2。根据免疫细胞组成,将总共353个TLS分为五个簇。其中,富Th型TLS在复发患者中显着增加(p = .0009)。这些数据表明,Th细胞占主导的组成可能会干扰抗肿瘤免疫反应,每种TLS的功能可能取决于其组成而有所不同。在多变量分析中,较高的Th细胞比例是疾病复发的最重要独立风险因素。Th细胞中增加的亚群是GATA3 + Th2。根据免疫细胞组成,将总共353个TLS分为五个簇。其中,富Th型TLS在复发患者中显着增加(p = .0009)。这些数据表明,Th细胞占主导的组成可能会干扰抗肿瘤免疫反应,每种TLS的功能可能取决于其组成而有所不同。
更新日期:2020-02-17
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