Cytotoxic tumour-infiltrating T lymphocytes influence outcome in resected pancreatic ductal adenocarcinoma

• Published in: European journal of cancer (1990) 2017-09, Vol.83, p.290-301
• Main Authors: 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.
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic - therapeutic use; Carcinoma, Pancreatic Ductal - immunology; Carcinoma, Pancreatic Ductal - pathology; Carcinoma, Pancreatic Ductal - therapy; CD103; CD103 antigen; CD3; CD3 antigen; CD3 Complex - metabolism; CD8; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cytotoxicity; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Disease-Free Survival; Female; Gemcitabine; Humans; Immunohistochemistry; Integrin beta4 - analysis; Lymphocytes; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - immunology; Male; Middle Aged; Pancreas; Pancreatic cancer; Pancreatic Neoplasms - immunology; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - therapy; Patients; Population studies; Prognosis; Standardization; Subpopulations; Survival; T lymphocytes; T-Lymphocytes, Cytotoxic - immunology; Tumors; Tumour-infiltrating lymphocytes
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2017.06.016

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. •The prognostic effects of lymphocyte subpopulations were studied in patients with pancreatic carcinoma (PDAC).•A high number of CD8-positive lymphocytes are associated with longer in PDAC.•The ratio of intraepithelial to total CD103-positive lymphocytes is associated with longer DFS and OS in PDAC.