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Clinical Impact of Different Classes of Infiltrating T Cytotoxic and Helper Cells (Th1, Th2, Treg, Th17) in Patients with Colorectal Cancer

Authors :
Jérôme Galon
Franck Pagès
Patrick Bruneval
Wolf H. Fridman
Gabriela Bindea
Amos Kirilovsky
Marie Tosolini
Anne Berger
Tessa Fredriksen
Bernhard Mlecnik
Stéphanie Mauger
Source :
Cancer Research; Vol 71
Publication Year :
2011
Publisher :
AMER ASSOC CANCER RESEARCH, 2011.

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. Cancer Res; 71(4); 1263–71. ©2011 AACR.

Details

Language :
English
ISSN :
00085472
Volume :
71
Issue :
4
Database :
OpenAIRE
Journal :
Cancer Research
Accession number :
edsair.doi.dedup.....da5f62970abdefcb65154dee54b67fc5
Full Text :
https://doi.org/10.1158/0008-5472.CAN-10-2907