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Increased tumor infiltration by mucosal-associated invariant T cells correlates with poor survival in colorectal cancer patients

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Abstract

The infiltration of tumors by lymphocytes is a prognosis factor in colorectal cancer (CRC). The magnitude and quality of this infiltration have emerged as important component of the clinical outcome in these patients. Specifically, markers associated with functional cell-mediated immunity, i.e., a Th1 immune response, are independent markers of better prognosis, whereas Th17-associated components are deleterious and correlate with poorer survival. Mucosal-associated invariant T (MAIT) cells are a recently described T cell subset with tissue-homing properties. They display a restricted TCR repertoire specific for widely conserved microbial ligands, and display anti-bacterial properties upon release of Th1-like, Th17-like, and/or cytotoxic granules. MAIT-cell-specific transcripts have been found in kidney and brain cancer, but have not been studies in other sites. In this study, we retrospectively analyzed by confocal microscopy the presence of MAIT cells within colorectal tumors as compared with paired healthy tissues. We observed a significant although variable increase, both in density and in proportion of overall tumor-infiltrating T lymphocytes inside the tumors. Importantly, survival curves as well as multivariate analysis showed that patients displaying a higher recruitment of MAIT cells in their tumor, as compared with the neighboring healthy tissue, showed a less favorable clinical outcome. This study suggests that including MAIT-cell-specific markers or transcripts in the analysis of tumor-infiltrating lymphocytes could be a benefit to the diagnosis and follow-up of CRC patients.

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Abbreviations

CD:

Crohn’s disease

CNS:

Central nervous system

CRC:

Colorectal cancer

DFS:

Disease-free survival

MAIT:

Mucosal-associated invariant T cells

MR1:

MHC-related 1

MS:

Multiple sclerosis

RORγt:

RAR-related orphan receptor gamma t

OS:

Overall survival

TIL:

Tumor-infiltrating lymphocytes

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Acknowledgments

E. Treiner wishes to thank Dr. François Vergez for help with statistical analysis. This work was funded by Conseil Régional de Picardie and the Fonds Européen de Développement Economique et Régional (FEDER).

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Author notes

  1. Emmanuel Treiner

    Present address: Inserm UMR1043, CHU Purpan, BP 3028, 31024, Toulouse Cedex 03, France

Authors and Affiliations

  1. EA4666, University of Picardie-Jules Verne, Amiens, France

    Luciane Zabijak, Caroline Guignant, Jean-Pierre Marolleau & Emmanuel Treiner

  2. ICAP Platform, University of Picardie-Jules Verne, Amiens, France

    Luciane Zabijak & Paulo Marcelo

  3. Immunology Laboratory, CHU Amiens, Amiens, France

    Caroline Guignant & Emmanuel Treiner

  4. Pathology Department, CHU Amiens, Amiens, France

    Christophe Attencourt & Denis Chatelain

  5. Hematology Department, CHU Amiens, Amiens, France

    Jean-Pierre Marolleau

Authors
  1. Luciane Zabijak
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  2. Christophe Attencourt
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Correspondence to Emmanuel Treiner.

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Zabijak, L., Attencourt, C., Guignant, C. et al. Increased tumor infiltration by mucosal-associated invariant T cells correlates with poor survival in colorectal cancer patients. Cancer Immunol Immunother 64, 1601–1608 (2015). https://doi.org/10.1007/s00262-015-1764-7

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  • DOI: https://doi.org/10.1007/s00262-015-1764-7

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