title: Tumor-reactive CD4+ CD8αβ+ CD103+ αβT cells: a prevalent tumor-reactive T-cell subset in metastatic colorectal cancers.
abstract: High level of T-cell infiltration in colorectal carcinomas (CRCs) is a good prognostic indicator, but the tumor reactivity of this infiltrate (tumor infiltrating lymphocytes [TIL]) is poorly documented. This study examined the presence, phenotype and functional features of tumor-reactive lymphocytes in human CRC. Freshly dissociated TIL and T cell lines were isolated from CRC samples and from some paired normal colonic mucosa. Four tumor cell lines were obtained. Autologous tumor reactivity of CRC TIL and tumor-reactive cell features were analyzed. We demonstrate the presence among CRC TIL of variable fractions (up to 18%) of double positive CD4(+) CD8αβ(+) (DP) αβ T cells. Interestingly, a high proportion (16-20%) of this TIL subset displayed tumor reactivity, whilst this was the case for no or few single positive TIL. Low levels of DP TIL were found in most CRC samples and in normal colonic mucosa, but these cells were higher in metastatic CRC. Furthermore, we showed that DP TIL were polyclonal, restricted by HLA class-I, proliferated poorly and secreted higher amounts of IL-4 and IL-13 than single positive T cells, on cognate or CD3 stimulation. DP CRC TIL also expressed CD103, confirming their mucosal origin. Increased frequencies of tumor-reactive DP TIL in metastatic CRC suggest that these cells play a role in the metastatic process of this cancer. Based on their high secretion of IL-4 and IL-13 and on previously described roles of these cytokines in cancers, we postulate that DP TIL could favor CRC growth or metastasis and/or downmodulate immune responses to these tumors.
authors.affiliation: INSERM U892, F-44093 Nantes, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Sarrabayrouse
authors.forename: Murielle
authors.initials: M
authors.lastname: Corvaisier
authors.forename: Laure-Hélène
authors.initials: LH
authors.lastname: Ouisse
authors.forename: Céline
authors.initials: C
authors.lastname: Bossard
authors.forename: Bernard
authors.initials: B
authors.lastname: Le Mével
authors.forename: Lucien
authors.initials: L
authors.lastname: Potiron
authors.forename: Guillaume
authors.initials: G
authors.lastname: Meurette
authors.forename: Nadine
authors.initials: N
authors.lastname: Gervois
authors.forename: Francine
authors.initials: F
authors.lastname: Jotereau
mesh_terms: D015703:Antigens, CD / Q000276:immunology*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D009362:Neoplasm Metastasis; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015703:Antigens, CD