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

• DOI: 10.4161/onci.29256
• Publication Date: 2014-06-25T19:21:50Z
• Authors: Florence Boissièr...; Gwendal Lazennec; Hélène Frugier; Marta Jarlier; Lise Roca; Jacqueline Duffour; Emilie Du Paty; Daniel Laune; France Blanchard; Florence Le Pessot; Jean-Christophe S...; Frédéric Bibeau
• Keywords: chemokine; 610; colorectal cancer; [SDV.CAN]Life Sciences [q-bio]/Cancer; [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology; inflammation; cytokine; microsatellite instability; Original Research

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.