Cytotoxic tumour-infiltrating T lymphocytes influence outcome in resected pancreatic ductal adenocarcinoma. (September 2017)

• Record Type: Journal Article
• 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.
• Is Part Of: European journal of cancer. Volume 83(2017)
• Page Start: 290
• Page End: 301
• Publication Date: 2017-09
• Subjects: Pancreatic cancer -- Gemcitabine -- Tumour-infiltrating lymphocytes -- T lymphocytes -- CD3 -- CD103 -- CD8; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2017.06.016
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Background: 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. Methods: Immunohistochemical stainings on tissue microarrays (TMAs) against CD3, CD8 and CD103 were performed according to standard procedures. Results: 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. Conclusion: T-lymphocyte subpopulations might be prognostic in resectable PDAC but need standardization and verification by further studies. Highlights: 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.