Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer

Cancer Res. 2011 Feb 15;71(4):1263-71. doi: 10.1158/0008-5472.CAN-10-2907. Epub 2011 Feb 8.

Abstract

The tumor microenvironment includes a complex network of immune T-cell subpopulations. In this study, we systematically analyzed the balance between cytotoxic T cells and different subsets of helper T cells in human colorectal cancers and we correlated their impact on disease-free survival. A panel of immune related genes were analyzed in 125 frozen colorectal tumor specimens. Infiltrating cytotoxic T cells, Treg, Th1, and Th17 cells were also quantified in the center and the invasive margin of the tumors. By hierarchical clustering of a correlation matrix we identified functional clusters of genes associated with Th17 (RORC, IL17A), Th2 (IL4, IL5, IL13), Th1 (Tbet, IRF1, IL12Rb2, STAT4), and cytotoxicity (GNLY, GZMB, PRF1). Patients with high expression of the Th17 cluster had a poor prognosis, whereas patients with high expression of the Th1 cluster had prolonged disease-free survival. In contrast, none of the Th2 clusters were predictive of prognosis. Combined analysis of cytotoxic/Th1 and Th17 clusters improved the ability to discriminate relapse. In situ analysis of the density of IL17+ cells and CD8+ cells in tumor tissues confirmed the results. Our findings argue that functional Th1 and Th17 clusters yield opposite effects on patient survival in colorectal cancer, and they provide complementary information that may improve prognosis.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Carcinoma / diagnosis*
  • Carcinoma / genetics
  • Carcinoma / immunology
  • Carcinoma / mortality
  • Cohort Studies
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / mortality
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interleukin-4 / genetics
  • Interleukin-4 / metabolism
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Lymphocytes, Tumor-Infiltrating / pathology*
  • Lymphocytes, Tumor-Infiltrating / physiology
  • Microarray Analysis
  • Prognosis
  • Survival Analysis
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism
  • T-Lymphocytes, Cytotoxic / pathology*
  • T-Lymphocytes, Cytotoxic / physiology
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / metabolism
  • T-Lymphocytes, Helper-Inducer / pathology*
  • T-Lymphocytes, Helper-Inducer / physiology
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th1 Cells / pathology
  • Th1 Cells / physiology
  • Th17 Cells / immunology
  • Th17 Cells / metabolism
  • Th17 Cells / pathology
  • Th17 Cells / physiology
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Th2 Cells / pathology
  • Th2 Cells / physiology
  • Tissue Array Analysis

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL4 protein, human
  • Interleukin-4