Better prognosis of gastric cancer patients with high levels of tumor infiltrating lymphocytes is counteracted by PD-1 expression.
Better prognosis of gastric cancer patients with high levels of tumor infiltrating lymphocytes is counteracted by PD-1 expression.
复制标题
肿瘤浸润性淋巴细胞水平高的胃癌患者预后较好，PD-1的表达对预后有影响。
DOI：
10.1080/2162402x.2020.1824632
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发表时间：
2020-09-30
期刊：
影响因子：
7.2
通讯作者：
Treese C
中科院分区：
文献类型：
--
作者：
Pötzsch M;Berg E;Hummel M;Stein U;von Winterfeld M;Jöhrens K;Rau B;Daum S;Treese C
抗肿瘤免疫反应的预后潜力在胃食管连接部和胃部腺癌 (AGE/S) 中变得越来越重要，特别是在免疫检查点抑制剂的使用方面。这项研究首次在大型白种人队列中分析了肿瘤浸润淋巴细胞 (TIL) 和检查点抑制剂对 AGE/S 患者的预后影响。我们筛选了 1992 年至 2005 年间接受手术的 438 名未接受治疗的 AGE/S 患者的组织样本，在组织微阵列 (TMA) 中进行检查，并针对人 CD3、CD4、CD8、PD-1 和 PD-L1 进行染色。在 438 个组织样本中，有 210 个适合进行多变量分析。这表明 CD3+、CD4+ 或 CD8+ TIL 的高浸润与 AGE/S 患者的总生存期增加相关，这只能在 CD3 的多变量分析中得到证实（HR：0.326；p = .023）。只要 TIL 不表达 PD-1，独立生存率的改善仅限于胃癌患者和早期肿瘤阶段（HR：1.522；p = .021）。亚组分析表明，TIL 依赖性抗肿瘤免疫反应仅对 PD-1 阴性 TIL 处于疾病早期的胃癌患者有效。 PD-1 和 CD3 的联合分析可以作为胃癌患者临床结果的预后标志物，也可能对免疫治疗有意义。
The prognostic potential of anti-tumor immune responses is becoming increasingly important in adenocarcinoma of the gastroesophageal junction and stomach (AGE/S) especially regarding the use of immune checkpoint inhibitors. This study analyzes for the first time the prognostic impact of tumor-infiltrating lymphocytes (TILs) and checkpoint inhibitors in a large Caucasian cohort in patients with AGE/S. We screened tissue samples from 438 therapy-naïve patients with AGE/S undergoing surgery between 1992 and 2005, examined in a tissue microarray (TMA) and stained against human CD3, CD4, CD8, PD-1, and PD-L1. Out of 438 tissue samples, 210 were eligible for multivariate analysis. This revealed that high infiltration with CD3+, CD4+, or CD8+ TILs was associated with an increased overall survival in AGE/S patients, which could only be confirmed in multivariate analysis for CD3 (HR: 0.326; p = .023). Independent improved survival was limited to gastric cancer patients and to early tumor stages as long as TILs did not express PD-1 (HR: 1.522; p = .021). Subgroup analyses indicate that TIL-dependent anti-tumor immune response is only effective in gastric cancer patients in early stages of disease in PD-1 negative TILs. Combined analysis of PD-1 and CD3 could serve as a prognostic marker for the clinical outcome of gastric cancer patients and could also be of interest for immunotherapy.