Cancer Immunology, Immunotherapy

, Volume 60, Issue 6, pp 869–882

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

  • Mónica Bernal
  • Angel Concha
  • Pablo Sáenz-López
  • Ana Isabel Rodríguez
  • Teresa Cabrera
  • Federico Garrido
  • Francisco Ruiz-Cabello
Original Article



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).


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).


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.


Gastrointestinal adenocarcinomas (GIACs) Microsatellite instability (MSI) HLA class I Tumor leukocyte infiltrate 



Antigen processing machinery


Colorectal cancer


Gastrointestinal adenocarcinoma


Human leukocyte antigen


Loss of heterozygosity


Major histocompatibility complex


Mismatch repair


Microsatellite instability


High microsatellite instability, MSS, microsatellite stability


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Mónica Bernal
    • 1
  • Angel Concha
    • 2
  • Pablo Sáenz-López
    • 1
  • Ana Isabel Rodríguez
    • 1
  • Teresa Cabrera
    • 1
    • 3
  • Federico Garrido
    • 1
    • 3
  • Francisco Ruiz-Cabello
    • 1
    • 3
  1. 1.Servicio de Análisis Clínicos e InmunologíaHospital Universitario Virgen de las NievesGranadaSpain
  2. 2.Servicio de Anatomía PatológicaHospital Universitario Virgen de las NievesGranadaSpain
  3. 3.Departamento de Bioquímica, Biología Molecular III e Inmunología, Facultad de MedicinaGranadaSpain

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