Spatial heterogeneity of the T cell receptor repertoire reflects the mutational landscape in lung cancer.

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ID: 62711
2019
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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.
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joshi2019spatialnature Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Joshi, Kroopa;Robert de Massy, Marc;Ismail, Mazlina;Reading, James L;Uddin, Imran;Woolston, Annemarie;Hatipoglu, Emine;Oakes, Theres;Rosenthal, Rachel;Peacock, Thomas;Ronel, Tahel;Noursadeghi, Mahdad;Turati, Virginia;Furness, Andrew J S;Georgiou, Andrew;Wong, Yien Ning Sophia;Ben Aissa, Assma;Werner Sunderland, Mariana;Jamal-Hanjani, Mariam;Veeriah, Selvaraju;Birkbak, Nicolai J;Wilson, Gareth A;Hiley, Crispin T;Ghorani, Ehsan;Guerra-Assunção, José Afonso;Herrero, Javier;Enver, Tariq;Hadrup, Sine R;Hackshaw, Allan;Peggs, Karl S;McGranahan, Nicholas;Swanton, Charles;, ;Quezada, Sergio A;Chain, Benny;
Journal Nature Medicine
Year 2019
DOI
10.1038/s41591-019-0592-2
URL
Keywords
transcriptome small rna hfq pyoverdine term-seq

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