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

Eur J Cancer. 2017 Sep:83:290-301. doi: 10.1016/j.ejca.2017.06.016. Epub 2017 Jul 31.

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.

Keywords: CD103; CD3; CD8; Gemcitabine; Pancreatic cancer; T lymphocytes; Tumour-infiltrating lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / therapeutic use
  • CD3 Complex / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • Carcinoma, Pancreatic Ductal / immunology*
  • Carcinoma, Pancreatic Ductal / pathology
  • Carcinoma, Pancreatic Ductal / therapy
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Disease-Free Survival
  • Female
  • Gemcitabine
  • Humans
  • Integrin beta4 / analysis
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / immunology*
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy
  • Prognosis
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Antimetabolites, Antineoplastic
  • CD3 Complex
  • Integrin beta4
  • Deoxycytidine
  • Gemcitabine