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Lymphocyte activation gene-3 (LAG3) mRNA and protein expression on tumour infiltrating lymphocytes (TILs) in oesophageal adenocarcinoma.

食管腺癌中淋巴细胞活化基因-3 (LAG3) mRNA和蛋白在肿瘤浸润淋巴细胞 (TILs) 上的表达。

  • 影响因子:3.23
  • DOI:10.1007/s00432-020-03295-7
  • 作者列表:"Gebauer F","Krämer M","Bruns C","Schlößer HA","Thelen M","Lohneis P","Schröder W","Zander T","Alakus H","Buettner R","Loeser H","Quaas A
  • 发表时间:2020-09-01
Abstract

PURPOSE:Lymphocyte activation gene-3 (LAG3) is an immunosuppressive checkpoint molecule expressed on T cells. The frequency and distribution of LAG3 expression in oesophageal adenocarcinoma (EAC) is unknown. Aim of the study was the evaluation and distribution of LAG3 on tumour infiltrating lymphocytes (TILs) and correlation with clinico-pathological and molecular data. METHODS:We analysed tumor tissue samples using immunohistochemistry, multi-colour immunofluorescence and mRNA in-situ technology. The analyses were performed on a multi-spot tissue microarray (TMA) with 165 samples, followed by an evaluation on a single-spot TMA with 477 samples. These results were correlated with clinical and molecular tumour data. RESULTS:LAG3 expression on TILs was detectable in 10.5% on the multi-spot TMA and 11.4% on the single-spot TMA. There was a strong correlation between protein expression and mRNA expression (p < 0.001) in TILs. LAG 3 expression was correlated with CD4+ and CD8+ T-cells within the tumor (p < 0.001). LAG3 expression showed an improved overall survival (OS) compared to patients without LAG3 expression (median OS 70.2 vs. 26.9 months; p = 0.046). The effect was even clearer in the group of patients with tumour stages > pT2 (70.2 vs 25.0 months; p = 0.037). CONCLUSION:This is the first description of LAG3 expression on TILs in EAC, underscoring the importance of immunomodulation in EAC. Our data suggest an impact of LAG3 in a relevant subset of EAC. Therapeutic studies investigating the efficacy of LAG3 inhibition in EAC will also provide predictive evidence and relevance of the immunohistochemical determination of LAG3 expression.

摘要

目的: 淋巴细胞活化基因-3 (LAG3) 是一种在T细胞上表达的免疫抑制检查点分子。LAG3在食管腺癌 (EAC) 中的表达频率和分布是未知的。本研究的目的是评估LAG3在肿瘤浸润淋巴细胞 (TILs) 上的分布以及与临床病理和分子数据的相关性。 方法: 采用免疫组织化学、多色免疫荧光和mRNA原位技术对肿瘤组织标本进行分析。在具有165个样品的多点组织微阵列 (TMA) 上进行分析,随后在具有477个样品的单点TMA上进行评估。这些结果与临床和分子肿瘤数据相关。 结果: 在多点TMA中10.5% 和在单点TMA中11.4% 可检测到til上的LAG3表达。Til中蛋白表达与mRNA表达之间存在强相关性 (p <0.001)。LAG 3表达与肿瘤内CD4 +  和CD8 + T T细胞相关 (p <0.001)。与无LAG3表达的患者相比,LAG3表达显示改善的总生存期 (OS) (中位OS 70.2个月vs. 26.9个月; P = 0.046)。在肿瘤分期> ptpt2的患者组中,效果更加明显 (70.2个月vs 25.0个月; P   =   0.037)。 结论: 这是对EAC中til上LAG3表达的首次描述,强调了EAC中免疫调节的重要性。我们的数据表明LAG3在EAC的相关子集中的影响。研究在EAC中LAG3抑制的功效的治疗性研究也将提供LAG3表达的免疫组织化学测定的预测性证据和相关性。

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影响因子:0.85
发表时间:2020-01-02
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DOI:10.1093/labmed/lmz021
作者列表:["Gannett MS","Gammon RR"]

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