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

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 in...

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Published in:Oncoimmunology Vol. 3; no. 6; p. e29256
Main Authors: Boissière-Michot, Florence, Lazennec, Gwendal, Frugier, Hélène, Jarlier, Marta, Roca, Lise, Duffour, Jacqueline, Du Paty, Emilie, Laune, Daniel, Blanchard, France, Le Pessot, Florence, Sabourin, Jean-Christophe, Bibeau, Frédéric
Format: Journal Article
Language:English
Published: United States Taylor & Francis 01.06.2014
Landes Bioscience
Subjects:
Adaptive immunology
Cancer
chemokine
colorectal cancer
cytokine
Human health and pathology
Hépatology and Gastroenterology
Immunology
inflammation
Life Sciences
microsatellite instability
Original Research
cytokine
microsatellite instability
chemokine
colorectal cancer
inflammation
ISSN:2162-402X, 2162-4011, 2162-402X
Online Access:Get full text
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Summary: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.
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These authors contributed equally to this work.
ISSN:2162-402X
2162-4011
2162-402X
DOI:10.4161/onci.29256