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High‐throughput sequencing of T‐cell receptors reveals a homogeneous repertoire of tumour‐infiltrating lymphocytes in ovarian cancer
Author(s) -
Emerson Ryan O,
Sherwood Anna M,
Rieder Mark J,
Guenthoer Jamie,
Williamson David W,
Carlson Christopher S,
Drescher Charles W,
Tewari Muneesh,
Bielas Jason H,
Robins Harlan S
Publication year - 2013
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4260
Subject(s) - biology , t cell receptor , immune system , ovarian cancer , clone (java method) , tumor infiltrating lymphocytes , melanoma , t cell , repertoire , acquired immune system , cancer research , cancer , immunology , immunotherapy , gene , genetics , physics , acoustics
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. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.