These authors contributed equally to this work.
High-throughput sequencing of T-cell receptors reveals a homogeneous repertoire of tumour-infiltrating lymphocytes in ovarian cancer
Article first published online: 12 NOV 2013
Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 231, Issue 4, pages 433–440, December 2013
How to Cite
Emerson, R. O., Sherwood, A. M., Rieder, M. J., Guenthoer, J., Williamson, D. W., Carlson, C. S., Drescher, C. W., Tewari, M., Bielas, J. H. and Robins, H. S. (2013), High-throughput sequencing of T-cell receptors reveals a homogeneous repertoire of tumour-infiltrating lymphocytes in ovarian cancer. J. Pathol., 231: 433–440. doi: 10.1002/path.4260
Conflict of interest statement: CSC and HSR have consultancy, patents & royalties, and equity ownership with Adaptive Biotechnologies. ROE, AMS, MJR, and DWW have employment and equity ownership with Adaptive Biotechnologies.
- Issue published online: 12 NOV 2013
- Article first published online: 12 NOV 2013
- Accepted manuscript online: 11 SEP 2013 01:02PM EST
- Manuscript Accepted: 6 SEP 2013
- Manuscript Revised: 20 AUG 2013
- Manuscript Received: 16 JUL 2013
- T cells;
- high-throughput sequencing;
- tumour-infiltrating lymphocytes (TILs);
- tumour heterogeneity;
- ovarian carcinoma
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.