Lohneis Philipp, Sinn Marianne, Bischoff Sven, Jühling Anja, Pelzer Uwe, Wislocka Lilianna, Bahra Marcus, Sinn Bruno V, Denkert Carsten, Oettle Helmut, Bläker Hendrik, Riess Hanno, Jöhrens Korinna, Striefler Jana K
Universitätsmedizin Charité Berlin, Institute of Pathology, Charitéplatz 1, 10117 Berlin, Germany.
Universitätsmedizin Charité Berlin, CONKO Study Group, Department of Medical Oncology, Haematology and Tumorimmunology, Augustenburger Platz 1, 13353 Berlin, Germany.
Eur J Cancer. 2017 Sep;83:290-301. doi: 10.1016/j.ejca.2017.06.016. Epub 2017 Jul 31.
We studied the prognostic effect of CD3-, CD8- and CD103-positive T lymphocytes in a cohort of 165 patients with resected pancreatic ductal adenocarcinomas (PDACs) of the treatment group (adjuvant gemcitabine) and the untreated control group of the CONKO-001 study.
Immunohistochemical stainings on tissue microarrays (TMAs) against CD3, CD8 and CD103 were performed according to standard procedures.
A high number of CD8-positive lymphocytes were significantly and independently associated with longer disease-free survival (DFS) and overall survival (OS) in the overall study population. Median DFS/OS were 7.4/18.1 months for patients with a low number of CD8-positive intratumoural lymphocytes (≤42 per 1 mm tissue core) and 12.7/25.2 months for patients with high numbers (>42 per 1-mm tissue core; p = 0.008/0.020; HR 0.62/0.65). The ratio of intraepithelial to total CD103-positive lymphocytes, but not total numbers of CD103-positive lymphocytes or CD103-positive intraepithelial lymphocytes, was associated with significantly improved DFS and OS in the overall study population (p = 0.022/0.009). Median DFS/OS was 5.9/15.7 for patients with a ratio of intraepithelial to total CD103-positive intratumoural lymphocytes higher than 0.3 and 11.6/24.7 for patients with a lower ratio.
T-lymphocyte subpopulations might be prognostic in resectable PDAC but need standardization and verification by further studies.
我们在CONKO-001研究的治疗组（辅助吉西他滨治疗）和未治疗的对照组中的165例接受胰腺导管腺癌（PDAC）切除术的患者队列中，研究了CD3、CD8和CD103阳性T淋巴细胞的预后作用。
按照标准程序对组织微阵列（TMA）进行抗CD3、CD8和CD103的免疫组织化学染色。
在整个研究人群中，大量CD8阳性淋巴细胞与更长的无病生存期（DFS）和总生存期（OS）显著且独立相关。肿瘤内CD8阳性淋巴细胞数量少（每1毫米组织芯≤42个）的患者，中位DFS/OS为7.4/18.1个月；数量多（每1毫米组织芯>42个）的患者，中位DFS/OS为12.7/25.2个月（p = 0.008/0.020；HR 0.62/0.65）。在整个研究人群中，上皮内与总CD103阳性淋巴细胞的比例，而非CD103阳性淋巴细胞总数或CD103阳性上皮内淋巴细胞数，与显著改善的DFS和OS相关（p = 0.022/0.009）。肿瘤内上皮内与总CD103阳性淋巴细胞比例高于0.3的患者，中位DFS/OS为5.9/15.7个月；比例较低的患者，中位DFS/OS为11.6/24.7个月。
T淋巴细胞亚群可能对可切除的PDAC具有预后价值，但需要通过进一步研究进行标准化和验证。
