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

Joshi, K ; de Massy MR ; et al.
In: Nature medicine, Jg. 25 (2019-10-01), Heft 10, S. 1549
academicJournal

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.

Titel:
Spatial heterogeneity of the T cell receptor repertoire reflects the mutational landscape in lung cancer.
Autor/in / Beteiligte Person: Joshi, K ; de Massy MR ; Ismail, M ; Reading, JL ; Uddin, I ; Woolston, A ; Hatipoglu, E ; Oakes, T ; Rosenthal, R ; Peacock, T ; Ronel, T ; Noursadeghi, M ; Turati, V ; Furness, AJS ; Georgiou, A ; Wong, YNS ; Ben Aissa, A ; Sunderland, MW ; Jamal-Hanjani, M ; Veeriah, S ; Birkbak, NJ ; Wilson, GA ; Hiley, CT ; Ghorani, E ; Guerra-Assunção, JA ; Herrero, J ; Enver, T ; Hadrup, SR ; Hackshaw, A ; Peggs, KS ; McGranahan, N ; Swanton, C ; Quezada, SA ; Chain, B
Zeitschrift: Nature medicine, Jg. 25 (2019-10-01), Heft 10, S. 1549
Veröffentlichung: New York Ny : Nature Publishing Company ; <i>Original Publication</i>: New York, NY : Nature Pub. Co., [1995-, 2019
Medientyp: academicJournal
ISSN: 1546-170X (electronic)
DOI: 10.1038/s41591-019-0592-2
Schlagwort:
  • Aged
  • CD8-Positive T-Lymphocytes immunology
  • CD8-Positive T-Lymphocytes pathology
  • Carcinoma, Non-Small-Cell Lung immunology
  • Carcinoma, Non-Small-Cell Lung pathology
  • Carcinoma, Non-Small-Cell Lung therapy
  • Female
  • Humans
  • Lymphocytes, Tumor-Infiltrating immunology
  • Lymphocytes, Tumor-Infiltrating pathology
  • Male
  • Middle Aged
  • Mutation
  • Receptors, Antigen, T-Cell immunology
  • Carcinoma, Non-Small-Cell Lung genetics
  • Genetic Heterogeneity
  • Immunotherapy, Adoptive
  • Receptors, Antigen, T-Cell genetics
Sonstiges:
  • Nachgewiesen in: MEDLINE
  • Sprachen: English
  • Corporate Authors: TRACERx consortium
  • Publication Type: Journal Article; Research Support, Non-U.S. Gov't
  • Language: English
  • [Nat Med] 2019 Oct; Vol. 25 (10), pp. 1549-1559. <i>Date of Electronic Publication: </i>2019 Oct 07.
  • MeSH Terms: Genetic Heterogeneity* ; Immunotherapy, Adoptive* ; Carcinoma, Non-Small-Cell Lung / *genetics ; Receptors, Antigen, T-Cell / *genetics ; Aged ; CD8-Positive T-Lymphocytes / immunology ; CD8-Positive T-Lymphocytes / pathology ; Carcinoma, Non-Small-Cell Lung / immunology ; Carcinoma, Non-Small-Cell Lung / pathology ; Carcinoma, Non-Small-Cell Lung / therapy ; Female ; Humans ; Lymphocytes, Tumor-Infiltrating / immunology ; Lymphocytes, Tumor-Infiltrating / pathology ; Male ; Middle Aged ; Mutation ; Receptors, Antigen, T-Cell / immunology
  • Comments: Comment in: Nat Rev Clin Oncol. 2020 Jan;17(1):5. (PMID: 31645685) ; Erratum in: Nat Med. 2020 Jul;26(7):1148. (PMID: 32494063)
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  • Grant Information: FC001169 United Kingdom MRC_ Medical Research Council; 13-0316 United Kingdom AICR_ Worldwide Cancer Research; 20265 United Kingdom CRUK_ Cancer Research UK; FC001169 United Kingdom CRUK_ Cancer Research UK; 20764 United Kingdom CRUK_ Cancer Research UK; 24314 United Kingdom CRUK_ Cancer Research UK; 16463 United Kingdom CRUK_ Cancer Research UK; 19310 United Kingdom CRUK_ Cancer Research UK; 28990 United Kingdom CRUK_ Cancer Research UK; 22246 United Kingdom CRUK_ Cancer Research UK; FC001169 United Kingdom ARC_ Arthritis Research UK; 17786 United Kingdom CRUK_ Cancer Research UK; A17786 United Kingdom CRUK_ Cancer Research UK; 30025 United Kingdom CRUK_ Cancer Research UK; A22246 United Kingdom CRUK_ Cancer Research UK; MC_UP_1203/1 United Kingdom MRC_ Medical Research Council; 21999 United Kingdom CRUK_ Cancer Research UK; MR/M009033/1 United Kingdom MRC_ Medical Research Council; 25253 United Kingdom CRUK_ Cancer Research UK; 24956 United Kingdom CRUK_ Cancer Research UK; MR/N000838/1 United Kingdom MRC_ Medical Research Council; 211179/Z/18/Z United Kingdom WT_ Wellcome Trust; A20764 United Kingdom CRUK_ Cancer Research UK; 20466 United Kingdom CRUK_ Cancer Research UK; FC001169 United Kingdom WT_ Wellcome Trust; United Kingdom WT_ Wellcome Trust
  • Contributed Indexing: Investigator: C Swanton; M Jamal-Hanjani; A Georgiou; MW Sunderland; JL Reading; KS Peggs; E Ghorani; MR de Massy; E Hatipoglu; SA Quezada; B Chain; N McGranahan; A Hackshaw; CT Hiley; S Veeriah; R Rosenthal; GA Wilson; J Herrero; NJ Birkbak; Y Ngai; A Sharp; C Rodrigues; O Pressey; S Smith; N Gower; H Dhanda; TBK Watkins; M Escudero; A Stewart; A Rowan; J Goldman; P Van Loo; RK Stone; T Denner; E Nye; S Ward; E Lim; S Boeing; M Greco; MA Bakir; K Litchfield; J Nicod; C Puttick; K Enfield; E Colliver; B Campbell; C Abbosh; Y Wu; M Skrzypski; RE Hynds; T Marafioti; JA Hartley; P Gorman; HL Lowe; L Ensell; V Spanswick; A Karamani; D Moore; D Biswas; M Razaq; S Beck; A Huebner; M Dietzen; C Naceur-Lombardelli; MA Akther; H Zhai; N Kannu; E Manzano; SK Bola; E Hoxha; S Ogwuru; D Lawrence; M Hayward; N Panagiotopoulos; R George; D Patrini; M Falzon; E Borg; R Khiroya; A Ahmed; M Taylor; J Choudhary; P Shaw; SM Janes; M Forster; T Ahmad; SM Lee; D Carnell; R Mendes; J George; N Navani; D Papadatos-Pastos; M Scarci; E Bertoja; RCM Stephens; EM Hoogenboom; JW Holding; S Bandula; G Price; S Dubois-Marshall; K Kerr; S Palmer; H Cheyne; J Miller; K Buchan; M Chetty; M Khalil; V Ezhil; V Prakash; G Anand; S Khan; K Lau; M Sheaff; P Schmid; L Lim; J Conibear; R Schwarz; J Tugwood; J Pierce; C Dive; G Brady; DG Rothwell; F Chemi; E Kilgour; F Blackhall; L Priest; MG Krebs; P Crosbie; J Le Quesne; J Riley; L Primrose; L Martinson; N Carey; JA Shaw; D Fennell; A Nakas; S Rathinam; L Nelson; K Ryanna; M Tuffail; A Bajaj; J Brozik; F Morgan; M Kornaszewska; R Attanoos; H Adams; H Davies; M Carter; CR Lindsay; F Gomes; Z Szallasi; R Salgado; I Csabai; M Diossy; H Aerts; A Kirk; M Asif; J Butler; R Bilanca; N Kostoulas; M MacKenzie; M Wilcox; S Busacca; A Dawson; MR Lovett; M Shackcloth; S Feeney; J Asante-Siaw; J Gosney; A Leek; N Totten; JD Hodgkinson; R Waddington; J Rogan; K Moore; W Monteiro; H Marshall; KG Blyth; C Dick; A Kidd; E Lim; P De Sousa; S Jordan; A Rice; H Raubenheimer; H Bhayani; M Hamilton; L Ambrose; A Devaraj; H Chavan; S Begum; A Mani; D Kaniu; M Malima; S Booth; AG Nicholson; N Fernandes; JE Wallen; P Shah; S Danson; J Bury; J Edwards; J Hill; S Matthews; Y Kitsanta; J Rao; S Tenconi; L Socci; K Suvarna; F Kibutu; P Fisher; R Young; J Barker; F Taylor; K Lloyd; T Light; T Horey; D Papadatos-Pastos; P Russell; S Lock; K Gilbert; B Naidu; G Langman; A Robinson; H Bancroft; A Kerr; S Kadiri; C Ferris; G Middleton; M Djearaman; A Patel; C Ottensmeier; S Chee; B Johnson; A Alzetani; E Shaw; J Lester; Y Summers; R Califano; P Taylor; R Shah; P Krysiak; K Rammohan; E Fontaine; R Booton; M Evison; S Moss; J Novasio; L Joseph; P Bishop; A Chaturvedi; H Doran; F Granato; V Joshi; E Smith; A Montero
  • Substance Nomenclature: 0 (Receptors, Antigen, T-Cell)
  • Entry Date(s): Date Created: 20191009 Date Completed: 20200121 Latest Revision: 20240210
  • Update Code: 20240210
  • PubMed Central ID: PMC6890490

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