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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 6/2011

01-06-2011 | Original Article

Leukocyte infiltrate in gastrointestinal adenocarcinomas is strongly associated with tumor microsatellite instability but not with tumor immunogenicity

Authors: Mónica Bernal, Angel Concha, Pablo Sáenz-López, Ana Isabel Rodríguez, Teresa Cabrera, Federico Garrido, Francisco Ruiz-Cabello

Published in: Cancer Immunology, Immunotherapy | Issue 6/2011

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Abstract

Purpose

To analyze the correlation of genomic instability with leukocyte infiltrate in gastrointestinal carcinomas (GIACs) and with tumor immunogenicity, e.g., HLA class I cell surface expression defects and galectin-3 and PDL-1 expression.

Experimental design

Lymphocyte and macrophage infiltrations were immunohistochemically studied in HLA class I negative GIACs with sporadic high-level microsatellite instability (MSI-H) or microsatellite stability (MSS).

Results

Tumors with MSI-H were associated with the following: dense infiltration (CD45, P < 0.001); cytotoxic CD8-positive lymphocytes (P < 0.001); and a complete absence of HLA class I cell surface expression, due to inactivating β2-microglobulin (β2-m) mutation in 50% of cases. In contrast, HLA class I negative tumors with MSS were significantly associated with fewer CD8-positive lymphocytes. There was no association between microsatellite instability and other molecular features of the tumor cells, including expression of galectin-3. Finally, macrophage infiltrate in the tumors was not correlated with microsatellite instability or HLA class I cell surface expression (CD64, P = 0.63; CD163, P = 0.51).

Conclusions

Microsatellite instability appears to be the most important factor determining the composition, density, and localization of leukocyte infiltrate, which is independent of other molecular features such expression of HLA class I cells, galectin-3, or programmed death ligand-1. Accordingly, the strong intratumoral CD8+ T infiltration of MSI-H tumors may be produced by elevated levels of specific inflammatory chemokines in the tumor microenvironment.
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Metadata
Title
Leukocyte infiltrate in gastrointestinal adenocarcinomas is strongly associated with tumor microsatellite instability but not with tumor immunogenicity
Authors
Mónica Bernal
Angel Concha
Pablo Sáenz-López
Ana Isabel Rodríguez
Teresa Cabrera
Federico Garrido
Francisco Ruiz-Cabello
Publication date
01-06-2011
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 6/2011
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-011-0999-1

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