| Literature DB >> 31591606 |
Kroopa Joshi1,2, Marc Robert de Massy1, Mazlina Ismail3, James L Reading1, Imran Uddin3, Annemarie Woolston3, Emine Hatipoglu1,2, Theres Oakes3, Rachel Rosenthal4,5, Thomas Peacock3,6, Tahel Ronel3, Mahdad Noursadeghi3, Virginia Turati7, Andrew J S Furness1,2, Andrew Georgiou1, Yien Ning Sophia Wong1, Assma Ben Aissa1,4, Mariana Werner Sunderland1, Mariam Jamal-Hanjani4, Selvaraju Veeriah4, Nicolai J Birkbak8, Gareth A Wilson4,8, Crispin T Hiley4, Ehsan Ghorani1, José Afonso Guerra-Assunção5, Javier Herrero5, Tariq Enver9, Sine R Hadrup10, Allan Hackshaw4, Karl S Peggs1, Nicholas McGranahan4, Charles Swanton11,12, Sergio A Quezada13,14, Benny Chain15,16.
Abstract
Somatic mutations together with immunoediting drive extensive heterogeneity within non-small-cell lung cancer (NSCLC). Herein we examine heterogeneity of the T cell antigen receptor (TCR) repertoire. The number of TCR sequences selectively expanded in tumors varies within and between tumors and correlates with the number of nonsynonymous mutations. Expanded TCRs can be subdivided into TCRs found in all tumor regions (ubiquitous) and those present in a subset of regions (regional). The number of ubiquitous and regional TCRs correlates with the number of ubiquitous and regional nonsynonymous mutations, respectively. Expanded TCRs form part of clusters of TCRs of similar sequence, suggestive of a spatially constrained antigen-driven process. CD8+ tumor-infiltrating lymphocytes harboring ubiquitous TCRs display a dysfunctional tissue-resident phenotype. Ubiquitous TCRs are preferentially detected in the blood at the time of tumor resection as compared to routine follow-up. These findings highlight a noninvasive method to identify and track relevant tumor-reactive TCRs for use in adoptive T cell immunotherapy.Entities:
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Year: 2019 PMID： 31591606 PMCID： PMC6890490 DOI： 10.1038/s41591-019-0592-2
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440