Pötzsch M, Berg E, Hummel M, Stein U, von Winterfeld M, Jöhrens K, Rau B, Daum S, Treese C
Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Berlin, Germany.
Oncoimmunology. 2020 Sep 30;9(1):1824632. doi: 10.1080/2162402X.2020.1824632.
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; = .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; = .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.
抗肿瘤免疫反应的预后潜力在胃食管交界腺癌和胃癌（AGE/S）中变得越来越重要，尤其是在免疫检查点抑制剂的应用方面。本研究首次分析了肿瘤浸润淋巴细胞（TILs）和检查点抑制剂对一大组白种人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例未经治疗的AGE/S患者的组织样本，在组织微阵列（TMA）中进行检测，并针对人CD3、CD4、CD8、PD-1和PD-L1进行染色。在438个组织样本中，210个符合多变量分析条件。这表明，CD3、CD4或CD8 TILs的高浸润与AGE/S患者的总生存期增加相关，这仅在CD3的多变量分析中得到证实（HR：0.326；P = 0.023）。只要TILs不表达PD-1，独立的生存改善仅限于胃癌患者和早期肿瘤阶段（HR：1.522；P = 0.021）。亚组分析表明，TIL依赖的抗肿瘤免疫反应仅在疾病早期的PD-1阴性TILs的胃癌患者中有效。PD-1和CD3的联合分析可作为胃癌患者临床结局的预后标志物，也可能对免疫治疗有意义。
