Characterization of an adaptive immune response in microsatellite-instable colorectal cancer

Florence Boissière-Michot (1) , Gwendal Lazennec (2) , Hélène Frugier (3) , Marta Jarlier (3) , Lise Roca (3) , Jacqueline Duffour (4) , Emilie Du Paty (5) , Daniel Laune (6) , France Blanchard (7) , Florence Le Pessot (8) , Jean-Christophe Sabourin (7) , Frédéric Bibeau (1)

1 Laboratoire d'anatomo-pathologie
2 Sys2Diag - Sys2Diag-Modélisation et Ingénierie des Systèmes Complexes Biologiques pour le Diagnostic
3 ICM - Institut régional de Cancérologie de Montpellier
4 CRLC Val d'Aurelle-Paul Lamarque
5 SysDiag - Sysdiag-Modélisation et Ingénierie des Systèmes Complexes Biologiques pour le Diagnostic
6 IRIM - Institut de Recherche en Infectiologie de Montpellier
7 CHU Rouen
8 Service d'Hépato-Gastroentérologie [CHU Rouen]

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.

Mots clés: inflammation; microsatellite instability; cytokine; chemokine; colorectal cancer; inflammation

Domaines: Cancer; Hépatologie et Gastroentérologie; Immunité adaptative

Florence Boissière-Michot, Gwendal Lazennec, Hélène Frugier, Marta Jarlier, Lise Roca, et al.. Characterization of an adaptive immune response in microsatellite-instable colorectal cancer. OncoImmunology, 2014, 3 (6), pp.e29256. ⟨10.4161/onci.29256⟩. ⟨hal-02146604⟩