화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Nature, Vol.567, No.7749, 479-+, 2019
DOI10.1038/s41586-019-1032-7  Export Citation
Neoantigen-directed immune escape in lung cancer evolution
Rosenthal R, Cadieux EL, Salgado R, Al Bakir M, Moore DA, Hiley CT, Lund T, Tanic M, Reading JL, Joshi K, Henry JY, Ghorani E, Wilson GA, Birkbak NJ, Jamal-Hanjani M, Veeriah S, Szallasi Z, Loi S, Hellmann MD, Feber A, Chain B, Herrero J, Quezada SA, Demeulemeester J, Van Loo P, Beck S, McGranahan N, Swanton C, Swanton C, Jamal-Hanjani M, Veeriah S, Czyzewska-Khan J, Johnson D, Laycock J, Rosenthal R, Gorman P, Hynds RE, Wilson G, Birkbak NJ, Watkins TBK, McGranahan N, Escudero M, Stewart A, Loo P, Rowan A, Hiley C, Abbosh C, Goldman J, Stone RK, Denner T, Ward S, Nye E, Joshi K, Aissa A, Wong YNS, Georgiou A, Quezada S, Hartley JA, Lowe HL, Herrero J, Lawrence D, Hayward M, Panagiotopoulos N, Falzon M, Borg E, Marafioti T, Janes SM, Forster M, Ahmad T, Lee SM, Papadatos-Pastos D, Carnell D, Mendes R, George J, Ahmed A, Taylor M, Choudhary J, Summers Y, Califano R, Taylor P, Shah R, Krysiak P, Rammohan K, Fontaine E, Booton R, Evison M, Crosbie P, Moss S, Joseph L, Bishop P, Quinn AM, Doran H, Leek A, Harrison P, Moore K, Waddington R, Novasio J, Blackhall F, Rogan J, Smith E, Dive C, Tugwood J, Brady G, Rothwell DG, Pierce J, Gulati S, Naidu B, Langman G, Trotter S, Bancroft H, Kerr A, Kadiri S, Middleton G, Djearaman M, Fennell D, Shaw JA, Le Quesne J, Moore DA, Nakas A, Rathinam S, Monteiro W, Marshall H, Nelson L, Riley J, Primrose L, Martinson L, Anand G, Khan S, Nicolson M, Kerr K, Palmer S, Remmen H, Miller J, Buchan K, Chetty M, Gomersall L, Lester J, Morgan F, Adams H, Davies H, Kornaszewska M, Attanoos R, Lock S, MacKenzie M, Wilcox M, Bell H, Hackshaw A, Ngai Y, Smith S, Gower N, Ottensmeier C, Chee S, Johnson B, Alzetani A, Shaw E, Lim E, De Sousa P, Barbosa MT, Bowman A, Jordan S, Rice A, Raubenheimer H, Bhayani H, Hamilton M, Mensah N, Ambrose L, Devaraj A, Chavan H, Nicholson AG, Lau K, Sheaff M, Schmid P, Conibear J, Ezhil V, Prakash V, Russell P, Light T, Horey T, Danson S, Bury J, Edwards J, Hill J, Matthews S, Kitsanta Y, Suvarna K, Fisher P, Shackcloth M, Gosney J, Feeney S, Asante-Siaw J, Ryanna K, Dawson A, Tuffail M, Bajaj A, Brozik J, Walter H, Carey N, Price G, Gilbert K, Webb J, Patel A, Chaturvedi A, Granato F, Baker K, Carter M, Priest L, Krebs MG, Lindsay C, Gomes F, Chemie F, George R, Patrini D, Khiroya R, Shaw P, Skrzypski M, Sunderland MW, Reading JL, Beastall C, Mangal N, Peggs K, Lim E, Al-Bakir M, Navani N, Scarci M, Ensell L, Biswas D, Salgado R, Razaq M, Nicod J, Beck S, Lopez S, Huebner A, Dietzen M, Mourikis T, Adefila-Ideozu T, Begum S, Klein H, Mani A, Carvalho S, Kaniu D, Realingo C, Malima M, Booth S, Lim L, Rao J, Tenconi S, Socci L, Kibutu F, Agyemang M, Young R, Blyth KG, Dick C, Kirk A, Kidd A
The interplay between an evolving cancer and a dynamic immune microenvironment remains unclear. Here we analyse 258 regions from 88 early-stage, untreated non-small-cell lung cancers using RNA sequencing and histopathology-assessed tumour-infiltrating lymphocyte estimates. Immune infiltration varied both between and within tumours, with different mechanisms of neoantigen presentation dysfunction enriched in distinct immune microenvironments. Sparsely infiltrated tumours exhibited a waning of neoantigen editing during tumour evolution, indicative of historical immune editing, or copy-number loss of previously clonal neoantigens. Immune-infiltrated tumour regions exhibited ongoing immunoediting, with either loss of heterozygosity in human leukocyte antigens or depletion of expressed neoantigens. We identified promoter hypermethylation of genes that contain neoantigenic mutations as an epigenetic mechanism of immunoediting. Our results suggest that the immune microenvironment exerts a strong selection pressure in early-stage, untreated non-small-cell lung cancers that produces multiple routes to immune evasion, which are clinically relevant and forecast poor disease-free survival.