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Tumor-infiltrating lymphocytes in colorectal tumors display a diversity of T cell receptor sequences that differ from the T cells in adjacent mucosal tissue

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Abstract

Tumors from colorectal cancer (CRC) are generally immunogenic and commonly infiltrated with T lymphocytes. However, the details of the adaptive immune reaction to these tumors are poorly understood. We have accrued both colon tumor samples and adjacent healthy mucosal samples from 15 CRC patients to study lymphocytes infiltrating these tissues. We apply a method for detailed sequencing of T-cell receptor (TCR) sequences from tumor-infiltrating lymphocytes (TILs) in CRC tumors at high throughput to probe T-cell clones in comparison with the TCRs from adjacent healthy mucosal tissue. In parallel, we captured TIL counts using standard immunohistochemistry. The variation in diversity of the TIL repertoire was far wider than the variation of T-cell clones in the healthy mucosa, and the oligoclonality was higher on average in the tumors. However, the diversity of the T-cell repertoire in both CRC tumors and healthy mucosa was on average 100-fold lower than in peripheral blood. Using the TCR sequences to identify and track clones between mucosal and tumor samples, we determined that the immune response in the tumor is different than in the adjacent mucosal tissue, and the number of shared clones is not dependent on distance between the samples. Together, these data imply that CRC tumors induce a specific adaptive immune response, but that this response differs widely in strength and breadth between patients.

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Conflict of interest

Anna Sherwood, Ryan Emerson, and Cindy Desmarais have employment and stock options at Adaptive Biotechnologies. Harlan Robins has consults for Adaptive Biotechnologies and owns stock. Dominique Scherer, Nina Habermann, Katharina Buck, Jürgen Staffa, Niels Halama, Dirk Jaeger, Peter Schirmacher, Esther Herpel, Matthias Kloor, Alexis Ulrich, Martin Schneider, Cornelia M Ulrich declare that they do not have any conflict of interest.

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Authors and Affiliations

  1. Adaptive Biotechnologies, 1551 Eastlake Ave, Seattle, WA, 98102, USA

    Anna M. Sherwood, Ryan O. Emerson & Cindy Desmarais

  2. Department of Preventive Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Im Neuenheimer Feld 460, 69120, Heidelberg, Germany

    Dominique Scherer, Nina Habermann, Katharina Buck, Jürgen Staffa & Cornelia M. Ulrich

  3. National Center for Tumor Diseases, Medical Oncology, University of Heidelberg Medical Center, Heidelberg, Germany

    Niels Halama & Dirk Jaeger

  4. German Cancer Consortium (DKTK), Im Neuenheimer Feld 224, 69120, Heidelberg, Germany

    Niels Halama & Dirk Jaeger

  5. Department of General Pathology, Institute of Pathology, University Clinic of Heidelberg, Heidelberg, Germany

    Peter Schirmacher & Esther Herpel

  6. Department of Molecular Pathology, Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany

    Matthias Kloor

  7. Department of Surgery, University Clinic of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany

    Alexis Ulrich & Martin Schneider

  8. Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA

    Cornelia M. Ulrich & Harlan Robins

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  1. Anna M. Sherwood
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  2. Ryan O. Emerson
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  3. Dominique Scherer
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  4. Nina Habermann
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  8. Niels Halama
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  9. Dirk Jaeger
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  10. Peter Schirmacher
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  11. Esther Herpel
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  13. Alexis Ulrich
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  14. Martin Schneider
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  15. Cornelia M. Ulrich
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  16. Harlan Robins
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Corresponding author

Correspondence to Harlan Robins.

Additional information

Anna M. Sherwood, Ryan O. Emerson, and Dominique Scherer contributed equally to this work.

Cornelia M. Ulrich and Harlan Robins contributed equally to this work.

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Sherwood, A.M., Emerson, R.O., Scherer, D. et al. Tumor-infiltrating lymphocytes in colorectal tumors display a diversity of T cell receptor sequences that differ from the T cells in adjacent mucosal tissue. Cancer Immunol Immunother 62, 1453–1461 (2013). https://doi.org/10.1007/s00262-013-1446-2

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  • DOI: https://doi.org/10.1007/s00262-013-1446-2

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