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 CRC s and 62 MSS CRC s 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 CCL 5 (RANTES), CXCL 8 (IL-8), CXCL 9 (MIG), IL -1ß, CXCL 10 (IP-10), IL -16, CXCL 1 (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 CCL 5, CXCL 10, and CXCL 9, 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. © 2014 Landes Bioscience.