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Association of tumor-infiltrating T lymphocytes with intestinal-type gastric cancer molecular subtypes and outcome.
Virchows Archiv ( IF 3.5 ) Pub Date : 2020-09-21 , DOI: 10.1007/s00428-020-02932-3
Naziha Mansuri 1 , Eva-Maria Birkman 2 , Vanina D Heuser 1 , Minnamaija Lintunen 2 , Annika Ålgars 3 , Jari Sundström 2 , Raija Ristamäki 3 , Laura Lehtinen 1 , Olli Carpén 1, 4
Affiliation  

While host immune response is likely to be important for the prognosis of gastric cancer patients, detailed information on the T lymphocyte infiltration in different gastric cancer subtypes is lacking. Here, we studied the presence of CD3, CD8, and FOXP3 (Forkhead box p3) expressing T lymphocytes in a retrospective cohort of 190 intestinal gastric and gastroesophageal adenocarcinomas. The cancers represented four distinct molecular subtypes: Epstein-Barr virus–positive (EBV+), mismatch-repair-deficient (MMR-D), aberrant TP53, and the “other” subtype. The absolute numbers of CD3+, CD8+, and FOXP3+ T lymphocytes were analyzed in relation with these molecular subtypes and selected clinicopathological parameters. Overall, there was a large variation in the amount of infiltrating T lymphocyte in all molecular subtypes. Among the subtypes, EBV+ cancers differed from the other subtypes in increased lymphocyte infiltration and high CD8+/FOXP3+ ratio. While the TP53 aberrant subtype did not differ in the absolute amount of T lymphocyte, the ratio of CD8+/FOXP3+ and CD3+/FOXP3+ cells was highest in this subtype, possibly reflecting immunosuppression associated with genomic instability. Increased CD3+ and CD8+ T lymphocyte infiltrates were associated with better survival, and remained as independent prognostic factors in a multivariate analysis. This study is the first to investigate lymphocytic infiltration within four molecular subtypes of intestinal-type gastric cancer in a European cohort. The results provide an important addition to the current knowledge of T lymphocyte–dependent immune response in gastric cancer and its prognostic significance.



中文翻译:

肿瘤浸润 T 淋巴细胞与肠型胃癌分子亚型和结果的关联。

虽然宿主免疫反应可能对胃癌患者的预后很重要,但缺乏不同胃癌亚型中 T 淋巴细胞浸润的详细信息。在这里,我们研究了 190 例肠胃和胃食管腺癌的回顾性队列中表达 CD3、CD8 和 FOXP3(Forkhead box p3)的 T 淋巴细胞的存在。这些癌症代表四种不同的分子亚型:EB病毒阳性(EBV+)、错配修复缺陷(MMR-D)、异常TP53和“其他”亚型。分析 CD3+、CD8+ 和 FOXP3+ T 淋巴细胞的绝对数量与这些分子亚型和选定的临床病理学参数的关系。总体而言,所有分子亚型中浸润 T 淋巴细胞的数量存在很大差异。在这些亚型中,EBV+癌症与其他亚型的不同之处在于淋巴细胞浸润增加和CD8+/FOXP3+比率高。虽然 TP53 异常亚型的 T 淋巴细胞绝对量没有差异,但该亚型中 CD8+/FOXP3+ 和 CD3+/FOXP3+ 细胞的比例最高,可能反映了与基因组不稳定相关的免疫抑制。CD3+ 和 CD8+ T 淋巴细胞浸润增加与更好的生存相关,并且在多变量分析中仍然是独立的预后因素。这项研究是第一个在欧洲队列中调查肠型胃癌四种分子亚型的淋巴细胞浸润的研究。这些结果为目前对胃癌 T 淋巴细胞依赖性免疫反应及其预后意义的认识提供了重要补充。

更新日期:2020-09-21
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