Philipp Lohneis1, Marianne Sinn2, Sven Bischoff2, Anja Jühling2, Uwe Pelzer2, Lilianna Wislocka2, Marcus Bahra3, Bruno V Sinn4, Carsten Denkert4, Helmut Oettle5, Hendrik Bläker4, Hanno Riess2, Korinna Jöhrens4, Jana K Striefler2. 1. Universitätsmedizin Charité Berlin, Institute of Pathology, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: philipp.lohneis@charite.de. 2. Universitätsmedizin Charité Berlin, CONKO Study Group, Department of Medical Oncology, Haematology and Tumorimmunology, Augustenburger Platz 1, 13353 Berlin, Germany. 3. Universitätsmedizin Charité Berlin, Department of General, Visceral and Transplantation Surgery, Augustenburger Platz 1, 13353 Berlin, Germany. 4. Universitätsmedizin Charité Berlin, Institute of Pathology, Charitéplatz 1, 10117 Berlin, Germany. 5. Outpatient Department Hematology/Oncology, Friedrichstrasse 53, 88045 Friedrichshafen, Germany.
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.
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.
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