PMID- 29107330 OWN - NLM STAT- MEDLINE DCOM- 20171222 LR - 20240210 IS - 1097-4172 (Electronic) IS - 0092-8674 (Print) IS - 0092-8674 (Linking) VI - 171 IP - 6 DP - 2017 Nov 30 TI - Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution. PG - 1259-1271.e11 LID - S0092-8674(17)31185-6 [pii] LID - 10.1016/j.cell.2017.10.001 [doi] AB - Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. VIDEO ABSTRACT. CI - Copyright (c) 2017 The Francis Crick Institute. Published by Elsevier Inc. All rights reserved. FAU - McGranahan, Nicholas AU - McGranahan N AD - Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6BT, UK. Electronic address: nicholas.mcgranahan.10@ucl.ac.uk. FAU - Rosenthal, Rachel AU - Rosenthal R AD - Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6BT, UK. FAU - Hiley, Crispin T AU - Hiley CT AD - Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6BT, UK; Division of Cancer Studies, King's College London, Guy's Campus, London SE1 1UL, UK. FAU - Rowan, Andrew J AU - Rowan AJ AD - Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, 1 Midland Rd, London NW1 1AT, UK. FAU - Watkins, Thomas B K AU - Watkins TBK AD - Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, 1 Midland Rd, London NW1 1AT, UK. FAU - Wilson, Gareth A AU - Wilson GA AD - Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6BT, UK; Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, 1 Midland Rd, London NW1 1AT, UK. FAU - Birkbak, Nicolai J AU - Birkbak NJ AD - Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6BT, UK; Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, 1 Midland Rd, London NW1 1AT, UK. FAU - Veeriah, Selvaraju AU - Veeriah S AD - Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6BT, UK. FAU - Van Loo, Peter AU - Van Loo P AD - Cancer Genomics Laboratory, The Francis Crick Institute, 1 Midland Rd, London NW1 1AT, UK; Department of Human Genetics, University of Leuven, 3000 BE Leuven, Belgium. FAU - Herrero, Javier AU - Herrero J AD - Bill Lyons Informatics Centre, University College London Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6BT, UK. FAU - Swanton, Charles AU - Swanton C AD - Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6BT, UK; Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, 1 Midland Rd, London NW1 1AT, UK. Electronic address: charles.swanton@crick.ac.uk. CN - TRACERx Consortium LA - eng GR - 20613/CRUK_/Cancer Research UK/United Kingdom GR - FC001202/WT_/Wellcome Trust/United Kingdom GR - 23464/CRUK_/Cancer Research UK/United Kingdom GR - FC001169/CRUK_/Cancer Research UK/United Kingdom GR - 20465/CRUK_/Cancer Research UK/United Kingdom GR - 18892/CRUK_/Cancer Research UK/United Kingdom GR - 15951/CRUK_/Cancer Research UK/United Kingdom GR - 13462/CRUK_/Cancer Research UK/United Kingdom GR - 20275/CRUK_/Cancer Research UK/United Kingdom GR - 19310/CRUK_/Cancer Research UK/United Kingdom GR - FC001202/CRUK_/Cancer Research UK/United Kingdom GR - 22795/CRUK_/Cancer Research UK/United Kingdom GR - 19278/CRUK_/Cancer Research UK/United Kingdom GR - FC001202/ARC_/Arthritis Research UK/United Kingdom GR - MR/P024351/1/MRC_/Medical Research Council/United Kingdom GR - MC_UP_1203/1/MRC_/Medical Research Council/United Kingdom GR - 21999/CRUK_/Cancer Research UK/United Kingdom GR - 17891/CRUK_/Cancer Research UK/United Kingdom GR - 2013 RIF - SHAW/PANCREATICCANUK_/Pancreatic Cancer UK/United Kingdom GR - FC001169/ARC_/Arthritis Research UK/United Kingdom GR - 20466/CRUK_/Cancer Research UK/United Kingdom GR - FC001169/WT_/Wellcome Trust/United Kingdom GR - WT_/Wellcome Trust/United Kingdom GR - 20276/CRUK_/Cancer Research UK/United Kingdom GR - 17786/CRUK_/Cancer Research UK/United Kingdom PT - Journal Article DEP - 20171026 PL - United States TA - Cell JT - Cell JID - 0413066 RN - 0 (HLA Antigens) SB - IM CIN - Nat Rev Clin Oncol. 2018 Jan;15(1):5. PMID: 29134958 CIN - Cell. 2017 Nov 30;171(6):1252-1253. PMID: 29195070 CIN - J Thorac Dis. 2018 Mar;10 (3):1248-1252. PMID: 29708132 MH - Adult MH - Aged MH - Aged, 80 and over MH - Antigen Presentation MH - Carcinoma, Non-Small-Cell Lung/genetics/*immunology/pathology/therapy MH - Cohort Studies MH - Female MH - HLA Antigens/*genetics/immunology MH - Humans MH - Loss of Heterozygosity MH - Lung Neoplasms/genetics/*immunology/pathology/therapy MH - Male MH - Middle Aged MH - Mutation MH - Polymorphism, Single Nucleotide MH - *Tumor Escape PMC - PMC5720478 OTO - NOTNLM OT - bioinformatics OT - cancer evolution OT - chromosomal instability OT - copy number OT - heterogeneity OT - immune-editing OT - immune-escape OT - loss of heterozygosity OT - lung cancer OT - neoantigen FIR - Swanton, Charles IR - Swanton C FIR - Jamal-Hanjani, Mariam IR - Jamal-Hanjani M FIR - Veeriah, Selvaraju IR - Veeriah S FIR - Shafi, Seema IR - Shafi S FIR - Czyzewska-Khan, Justyna IR - Czyzewska-Khan J FIR - Johnson, Diana IR - Johnson D FIR - Laycock, Joanne IR - Laycock J FIR - Bosshard-Carter, Leticia IR - Bosshard-Carter L FIR - Rosenthal, Rachel IR - Rosenthal R FIR - Gorman, Pat IR - Gorman P FIR - Hynds, Robert E IR - Hynds RE FIR - Wilson, Gareth IR - Wilson G FIR - Birkbak, Nicolai J IR - Birkbak NJ FIR - Watkins, Thomas B K IR - Watkins TBK FIR - McGranahan, Nicholas IR - McGranahan N FIR - Horswell, Stuart IR - Horswell S FIR - Mitter, Richard IR - Mitter R FIR - Escudero, Mickael IR - Escudero M FIR - Stewart, Aengus IR - Stewart A FIR - Van Loo, Peter IR - Van Loo P FIR - Rowan, Andrew IR - Rowan A FIR - Xu, Hang IR - Xu H FIR - Turajlic, Samra IR - Turajlic S FIR - Hiley, Crispin IR - Hiley C FIR - Abbosh, Christopher IR - Abbosh C FIR - Goldman, Jacki IR - Goldman J FIR - Stone, Richard Kevin IR - Stone RK FIR - Denner, Tamara IR - Denner T FIR - Matthews, Nik IR - Matthews N FIR - Elgar, Greg IR - Elgar G FIR - Ward, Sophia IR - Ward S FIR - Costa, Marta IR - Costa M FIR - Begum, Sharmin IR - Begum S FIR - Phillimore, Ben IR - Phillimore B FIR - Chambers, Tim IR - Chambers T FIR - Nye, Emma IR - Nye E FIR - Graca, Sofia IR - Graca S FIR - Al Bakir, Maise IR - Al Bakir M FIR - Joshi, Kroopa IR - Joshi K FIR - Furness, Andrew IR - Furness A FIR - Ben Aissa, Assma IR - Ben Aissa A FIR - Wong, Yien Ning Sophia IR - Wong YNS FIR - Georgiou, Andy IR - Georgiou A FIR - Quezada, Sergio IR - Quezada S FIR - Hartley, John A IR - Hartley JA FIR - Lowe, Helen L IR - Lowe HL FIR - Herrero, Javier IR - Herrero J FIR - Lawrence, David IR - Lawrence D FIR - Hayward, Martin IR - Hayward M FIR - Panagiotopoulos, Nikolaos IR - Panagiotopoulos N FIR - Kolvekar, Shyam IR - Kolvekar S FIR - Falzon, Mary IR - Falzon M FIR - Borg, Elaine IR - Borg E FIR - Marafioti, Teresa IR - Marafioti T FIR - Simeon, Celia IR - Simeon C FIR - Hector, Gemma IR - Hector G FIR - Smith, Amy IR - Smith A FIR - Aranda, Marie IR - Aranda M FIR - Novelli, Marco IR - Novelli M FIR - Oukrif, Dahmane IR - Oukrif D FIR - Janes, Sam M IR - Janes SM FIR - Thakrar, Ricky IR - Thakrar R FIR - Forster, Martin IR - Forster M FIR - Ahmad, Tanya IR - Ahmad T FIR - Lee, Siow Ming IR - Lee SM FIR - Papadatos-Pastos, Dionysis IR - Papadatos-Pastos D FIR - Carnell, Dawn IR - Carnell D FIR - Mendes, Ruheena IR - Mendes R FIR - George, Jeremy IR - George J FIR - Navani, Neal IR - Navani N FIR - Ahmed, Asia IR - Ahmed A FIR - Taylor, Magali IR - Taylor M FIR - Choudhary, Junaid IR - Choudhary J FIR - Summers, Yvonne IR - Summers Y FIR - Califano, Raffaele IR - Califano R FIR - Taylor, Paul IR - Taylor P FIR - Shah, Rajesh IR - Shah R FIR - Krysiak, Piotr IR - Krysiak P FIR - Rammohan, Kendadai IR - Rammohan K FIR - Fontaine, Eustace IR - Fontaine E FIR - Booton, Richard IR - Booton R FIR - Evison, Matthew IR - Evison M FIR - Crosbie, Phil IR - Crosbie P FIR - Moss, Stuart IR - Moss S FIR - Idries, Faiza IR - Idries F FIR - Joseph, Leena IR - Joseph L FIR - Bishop, Paul IR - Bishop P FIR - Chaturved, Anshuman IR - Chaturved A FIR - Quinn, Anne Marie IR - Quinn AM FIR - Doran, Helen IR - Doran H FIR - Leek, Angela IR - Leek A FIR - Harrison, Phil IR - Harrison P FIR - Moore, Katrina IR - Moore K FIR - Waddington, Rachael IR - Waddington R FIR - Novasio, Juliette IR - Novasio J FIR - Blackhall, Fiona IR - Blackhall F FIR - Rogan, Jane IR - Rogan J FIR - Smith, Elaine IR - Smith E FIR - Dive, Caroline IR - Dive C FIR - Tugwood, Jonathan IR - Tugwood J FIR - Brady, Ged IR - Brady G FIR - Rothwell, Dominic G IR - Rothwell DG FIR - Chemi, Francesca IR - Chemi F FIR - Pierce, Jackie IR - Pierce J FIR - Gulati, Sakshi IR - Gulati S FIR - Naidu, Babu IR - Naidu B FIR - Langman, Gerald IR - Langman G FIR - Trotter, Simon IR - Trotter S FIR - Bellamy, Mary IR - Bellamy M FIR - Bancroft, Hollie IR - Bancroft H FIR - Kerr, Amy IR - Kerr A FIR - Kadiri, Salma IR - Kadiri S FIR - Webb, Joanne IR - Webb J FIR - Middleton, Gary IR - Middleton G FIR - Djearaman, Madava IR - Djearaman M FIR - Fennell, Dean IR - Fennell D FIR - Shaw, Jacqui A IR - Shaw JA FIR - Le Quesne, John IR - Le Quesne J FIR - Moore, David IR - Moore D FIR - Nakas, Apostolos IR - Nakas A FIR - Rathinam, Sridhar IR - Rathinam S FIR - Monteiro, William IR - Monteiro W FIR - Marshall, Hilary IR - Marshall H FIR - Nelson, Louise IR - Nelson L FIR - Bennett, Jonathan IR - Bennett J FIR - Riley, Joan IR - Riley J FIR - Primrose, Lindsay IR - Primrose L FIR - Martinson, Luke IR - Martinson L FIR - Anand, Girija IR - Anand G FIR - Khan, Sajid IR - Khan S FIR - Amadi, Anita IR - Amadi A FIR - Nicolson, Marianne IR - Nicolson M FIR - Kerr, Keith IR - Kerr K FIR - Palmer, Shirley IR - Palmer S FIR - Remmen, Hardy IR - Remmen H FIR - Miller, Joy IR - Miller J FIR - Buchan, Keith IR - Buchan K FIR - Chetty, Mahendran IR - Chetty M FIR - Gomersall, Lesley IR - Gomersall L FIR - Lester, Jason IR - Lester J FIR - Edwards, Alison IR - Edwards A FIR - Morgan, Fiona IR - Morgan F FIR - Adams, Haydn IR - Adams H FIR - Davies, Helen IR - Davies H FIR - Kornaszewska, Malgorzata IR - Kornaszewska M FIR - Attanoos, Richard IR - Attanoos R FIR - Lock, Sara IR - Lock S FIR - Verjee, Azmina IR - Verjee A FIR - MacKenzie, Mairead IR - MacKenzie M FIR - Wilcox, Maggie IR - Wilcox M FIR - Bell, Harriet IR - Bell H FIR - Hackshaw, Allan IR - Hackshaw A FIR - Ngai, Yenting IR - Ngai Y FIR - Smith, Sean IR - Smith S FIR - Gower, Nicole IR - Gower N FIR - Ottensmeier, Christian IR - Ottensmeier C FIR - Chee, Serena IR - Chee S FIR - Johnson, Benjamin IR - Johnson B FIR - Alzetani, Aiman IR - Alzetani A FIR - Shaw, Emily IR - Shaw E FIR - Lim, Eric IR - Lim E FIR - De Sousa, Paulo IR - De Sousa P FIR - Barbosa, Monica Tavares IR - Barbosa MT FIR - Bowman, Alex IR - Bowman A FIR - Jordan, Simon IR - Jordan S FIR - Rice, Alexandra IR - Rice A FIR - Raubenheimer, Hilgardt IR - Raubenheimer H FIR - Proli, Chiara IR - Proli C FIR - Cufari, Maria Elena IR - Cufari ME FIR - Ronquillo, John Carlo IR - Ronquillo JC FIR - Kwayie, Angela IR - Kwayie A FIR - Bhayani, Harshil IR - Bhayani H FIR - Hamilton, Morag IR - Hamilton M FIR - Bakar, Yusura IR - Bakar Y FIR - Mensah, Natalie IR - Mensah N FIR - Ambrose, Lyn IR - Ambrose L FIR - Devaraj, Anand IR - Devaraj A FIR - Buderi, Silviu IR - Buderi S FIR - Finch, Jonathan IR - Finch J FIR - Azcarate, Leire IR - Azcarate L FIR - Chavan, Hema IR - Chavan H FIR - Green, Sophie IR - Green S FIR - Mashinga, Hillaria IR - Mashinga H FIR - Nicholson, Andrew G IR - Nicholson AG FIR - Lau, Kelvin IR - Lau K FIR - Sheaff, Michael IR - Sheaff M FIR - Schmid, Peter IR - Schmid P FIR - Conibear, John IR - Conibear J FIR - Ezhil, Veni IR - Ezhil V FIR - Ismail, Babikir IR - Ismail B FIR - Irvin-Sellers, Melanie IR - Irvin-Sellers M FIR - Prakash, Vineet IR - Prakash V FIR - Russell, Peter IR - Russell P FIR - Light, Teresa IR - Light T FIR - Horey, Tracey IR - Horey T FIR - Danson, Sarah IR - Danson S FIR - Bury, Jonathan IR - Bury J FIR - Edwards, John IR - Edwards J FIR - Hill, Jennifer IR - Hill J FIR - Matthews, Sue IR - Matthews S FIR - Kitsanta, Yota IR - Kitsanta Y FIR - Suvarna, Kim IR - Suvarna K FIR - Fisher, Patricia IR - Fisher P FIR - Keerio, Allah Dino IR - Keerio AD FIR - Shackcloth, Michael IR - Shackcloth M FIR - Gosney, John IR - Gosney J FIR - Postmus, Pieter IR - Postmus P FIR - Feeney, Sarah IR - Feeney S FIR - Asante-Siaw, Julius IR - Asante-Siaw J FIR - Aerts, Hugo J W L IR - Aerts HJWL FIR - Dentro, Stefan IR - Dentro S FIR - Dessimoz, Christophe IR - Dessimoz C EDAT- 2017/11/07 06:00 MHDA- 2017/12/23 06:00 PMCR- 2017/11/30 CRDT- 2017/11/07 06:00 PHST- 2017/07/14 00:00 [received] PHST- 2017/09/06 00:00 [revised] PHST- 2017/09/28 00:00 [accepted] PHST- 2017/11/07 06:00 [pubmed] PHST- 2017/12/23 06:00 [medline] PHST- 2017/11/07 06:00 [entrez] PHST- 2017/11/30 00:00 [pmc-release] AID - S0092-8674(17)31185-6 [pii] AID - 10.1016/j.cell.2017.10.001 [doi] PST - ppublish SO - Cell. 2017 Nov 30;171(6):1259-1271.e11. doi: 10.1016/j.cell.2017.10.001. Epub 2017 Oct 26.