title: Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer.
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.
authors.affiliation: INSERM, Integrative Cancer Immunology Team, INSERM U872, Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Tosolini
authors.forename: Amos
authors.initials: A
authors.lastname: Kirilovsky
authors.forename: Bernhard
authors.initials: B
authors.lastname: Mlecnik
authors.forename: Tessa
authors.initials: T
authors.lastname: Fredriksen
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Mauger
authors.forename: Gabriela
authors.initials: G
authors.lastname: Bindea
authors.forename: Anne
authors.initials: A
authors.lastname: Berger
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruneval
authors.forename: Wolf-Herman
authors.initials: WH
authors.lastname: Fridman
authors.forename: Franck
authors.initials: F
authors.lastname: Pagès
authors.forename: Jérôme
authors.initials: J
authors.lastname: Galon
mesh_terms: D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000401:mortality; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000401:mortality; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D046228:Microarray Analysis; D011379:Prognosis; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D046888:Tissue Array Analysis
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508598:IL4 protein, human; D015847:Interleukin-4