title: T cell receptor repertoire usage in cancer as a surrogate marker for immune responses.
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.
authors.affiliation: Department of Dermatology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Schrama
authors.affiliation: Department of Translational Skin Cancer Research, University Hospital Essen, Essen, Germany.|German Cancer Consortium (DKTK), Essen, Germany.|German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Cathrin
authors.initials: C
authors.lastname: Ritter
authors.affiliation: Department of Translational Skin Cancer Research, University Hospital Essen, Essen, Germany. j.becker@dkfz.de.|German Cancer Consortium (DKTK), Essen, Germany. j.becker@dkfz.de.|German Cancer Research Center (DKFZ), Heidelberg, Germany. j.becker@dkfz.de.
authors.forename: Jürgen C
authors.initials: JC
authors.lastname: Becker
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D015415:Biomarkers; D014408:Biomarkers, Tumor; D060965:Clonal Evolution; D015329:Gene Rearrangement, T-Lymphocyte; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007157:Immunologic Surveillance; D007167:Immunotherapy; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000628:therapy; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D014408:Biomarkers, Tumor; D011948:Receptors, Antigen, T-Cell