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T cell receptor repertoire usage in cancer as a surrogate marker for immune responses

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Abstract

Characterizing the interaction of cancer cells with the host adaptive immune system is critical for understanding tumor immunology and the modus operandi of immunotherapeutic interventions to treat cancer. As the key cellular effectors of adaptive immunity, T cells are endowed with specialized receptors (the T cell receptor; TCR), to recognize and to eliminate cancer cells. The diversity of the TCR repertoire results from specialized genetic diversification mechanisms that generate an incredible variability allowing recognizing extensive collections of antigens. Based on the attainment and function of the TCR, the TCR repertoire is a mirror of the human immune response, and the dynamic changes of its usage can be assumed as a promising biomarker to monitor immunomodulatory therapies. Recent advances in multiplexed PCR amplification and massive parallel sequencing technologies have facilitated the characterization of TCR repertoires at high resolution even when only biomaterial of limited quantity and quality, such as formalin-fixed paraffin-embedded (FFPE) archived tissues, is available. Here, we review the concept framework and current experimental approaches to characterize the TCR repertoire usage in cancer including inherent technical and biological challenges.

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Authors and Affiliations

  1. Department of Dermatology, University Hospital Würzburg, Würzburg, Germany

    David Schrama

  2. Department of Translational Skin Cancer Research, University Hospital Essen, Essen, Germany

    Cathrin Ritter & Jürgen C. Becker

  3. German Cancer Consortium (DKTK), Essen, Germany

    Cathrin Ritter & Jürgen C. Becker

  4. German Cancer Research Center (DKFZ), Heidelberg, Germany

    Cathrin Ritter & Jürgen C. Becker

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  1. David Schrama
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  2. Cathrin Ritter
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  3. Jürgen C. Becker
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Correspondence to Jürgen C. Becker.

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This article is a contribution to the special issue on Cancer and Autoimmunity - Guest Editor: Mads Hald Andersen

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Schrama, D., Ritter, C. & Becker, J.C. T cell receptor repertoire usage in cancer as a surrogate marker for immune responses. Semin Immunopathol 39, 255–268 (2017). https://doi.org/10.1007/s00281-016-0614-9

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