title: Characterization of an adaptive immune response in microsatellite-instable colorectal cancer.
abstract: Sporadic or hereditary colorectal cancer (CRC) with microsatellite instability (MSI) is frequently characterized by inflammatory lymphocytic infiltration and tends to be associated with a better outcome than microsatellite stable (MSS) CRC, probably reflecting a more effective immune response. We investigated inflammatory mechanisms in 48 MSI CRCs and 62 MSS CRCs by analyzing: (1) the expression of 48 cytokines using Bio-Plex multiplex cytokine assays, and (2) the in situ immune response by immunohistochemical analysis with antibodies against CD3 (T lymphocytes), CD8 (cytotoxic T lymphocytes), CD45RO (memory T lymphocytes), T-bet (Th1 CD4 cells), and FoxP3 (regulatory T cells). MSI CRC exhibited significantly higher expression of CCL5 (RANTES), CXCL8 (IL-8), CXCL9 (MIG), IL-1β, CXCL10 (IP-10), IL-16, CXCL1 (GROα), and IL-1ra, and lower expression of MIF, compared with MSS CRC. Immunohistochemistry combined with image analysis indicated that the density of CD3+, CD8+, CD45RO+, and T-bet+T lymphocytes was higher in MSI CRC than in MSS CRC, whereas the number of regulatory T cells (FoxP3+) was not statistically different between the groups. These results indicate that MSI CRC is associated with a specific cytokine expression profile that includes CCL5, CXCL10, and CXCL9, which are involved in the T helper type 1 (Th1) response and in the recruitment of memory CD45RO+T cells. Our findings highlight the major role of adaptive immunity in MSI CRC and provide a possible explanation for the more favorable prognosis of this CRC subtype.
authors.affiliation: Pathology Department, Institut régional du Cancer de Montpellier (ICM)-Val d'Aurelle; Montpellier, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Boissière-Michot
authors.affiliation: UMR 3145 SYSDIAG CNRS; Montpellier, France.
authors.forename: Gwendal
authors.initials: G
authors.lastname: Lazennec
authors.affiliation: Pathology Department, Institut régional du Cancer de Montpellier (ICM)-Val d'Aurelle; Montpellier, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Frugier
authors.affiliation: Biostatistics Department, Institut régional du Cancer de Montpellier (ICM)-Val d'Aurelle; Montpellier, France.
authors.forename: Marta
authors.initials: M
authors.lastname: Jarlier
authors.affiliation: Biostatistics Department, Institut régional du Cancer de Montpellier (ICM)-Val d'Aurelle; Montpellier, France.
authors.forename: Lise
authors.initials: L
authors.lastname: Roca
authors.affiliation: Oncology Department, Institut régional du Cancer de Montpellier (ICM)-Val d'Aurelle; Montpellier, France.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Duffour
authors.affiliation: UMR 3145 SYSDIAG CNRS; Montpellier, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Du Paty
authors.affiliation: UMR 3145 SYSDIAG CNRS; Montpellier, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Laune
authors.affiliation: University Hospital; Rouen, France.
authors.forename: France
authors.initials: F
authors.lastname: Blanchard
authors.affiliation: University Hospital; Rouen, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Le Pessot
authors.affiliation: University Hospital; Rouen, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Sabourin
authors.affiliation: Pathology Department, Institut régional du Cancer de Montpellier (ICM)-Val d'Aurelle; Montpellier, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bibeau
keywords: chemokine; colorectal cancer; cytokine; inflammation; microsatellite instability
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