title: High-throughput sequencing of T-cell receptors reveals a homogeneous repertoire of tumour-infiltrating lymphocytes in ovarian cancer.
abstract: The cellular adaptive immune system mounts a response to many solid tumours mediated by tumour-infiltrating T lymphocytes (TILs). Basic measurements of these TILs, including total count, show promise as prognostic markers for a variety of cancers, including ovarian and colorectal. In addition, recent therapeutic advances are thought to exploit this immune response to effectively fight melanoma, with promising studies showing efficacy in additional cancers. However, many of the basic properties of TILs are poorly understood, including specificity, clonality, and spatial heterogeneity of the T-cell response. We utilize deep sequencing of rearranged T-cell receptor beta (TCRB) genes to characterize the basic properties of TILs in ovarian carcinoma. Due to somatic rearrangement during T-cell development, the TCR beta chain sequence serves as a molecular tag for each T-cell clone. Using these sequence tags, we assess similarities and differences between infiltrating T cells in discretely sampled sections of large tumours and compare to T cells from peripheral blood. Within the limits of sensitivity of our assay, the TIL repertoires show strong similarity throughout each tumour and are distinct from the circulating T-cell repertoire. We conclude that the cellular adaptive immune response within ovarian carcinomas is spatially homogeneous and distinct from the T-cell compartment of peripheral blood.
authors.affiliation: Adaptive Biotechnologies, Seattle, WA.
authors.forename: Ryan O
authors.initials: RO
authors.lastname: Emerson
authors.affiliation: Adaptive Biotechnologies, Seattle, WA.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Sherwood
authors.affiliation: Adaptive Biotechnologies, Seattle, WA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Rieder
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Guenthoer
authors.affiliation: Adaptive Biotechnologies, Seattle, WA.
authors.forename: David W
authors.initials: DW
authors.lastname: Williamson
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Carlson
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA.|University of Washington School of Medicine, Seattle, WA.
authors.forename: Charles W
authors.initials: CW
authors.lastname: Drescher
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA.|University of Washington School of Medicine, Seattle, WA.
authors.forename: Muneesh
authors.initials: M
authors.lastname: Tewari
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Jason H
authors.initials: JH
authors.lastname: Bielas
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Harlan S
authors.initials: HS
authors.lastname: Robins
mesh_terms: D056704:Adaptive Immunity; D016000:Cluster Analysis; D022801:Complementarity Determining Regions / Q000235:genetics; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000276:immunology; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D009852:Omentum; D010051:Ovarian Neoplasms / Q000235:genetics / Q000276:immunology*; D010534:Peritoneal Neoplasms / Q000276:immunology / Q000556:secondary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods
chemical_list: D022801:Complementarity Determining Regions; D016693:Receptors, Antigen, T-Cell, alpha-beta
keywords: T cells; high-throughput sequencing; ovarian carcinoma; tumour heterogeneity; tumour-infiltrating lymphocytes (TILs)
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