Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution.
Details
Serval ID
serval:BIB_FAC182E4CFA0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution.
Journal
Cell
Working group(s)
TRACERx Consortium
Contributor(s)
Swanton C., Jamal-Hanjani M., Veeriah S., Shafi S., Czyzewska-Khan J., Johnson D., Laycock J., Bosshard-Carter L., Rosenthal R., Gorman P., Hynds R.E., Wilson G., Birkbak N.J., Watkins TBK, McGranahan N., Horswell S., Mitter R., Escudero M., Stewart A., Van Loo P., Rowan A., Xu H., Turajlic S., Hiley C., Abbosh C., Goldman J., Stone R.K., Denner T., Matthews N., Elgar G., Ward S., Costa M., Begum S., Phillimore B., Chambers T., Nye E., Graca S., Al Bakir M., Joshi K., Furness A., Ben Aissa A., Wong YNS, Georgiou A., Quezada S., Hartley J.A., Lowe H.L., Herrero J., Lawrence D., Hayward M., Panagiotopoulos N., Kolvekar S., Falzon M., Borg E., Marafioti T., Simeon C., Hector G., Smith A., Aranda M., Novelli M., Oukrif D., Janes S.M., Thakrar R., Forster M., Ahmad T., Lee S.M., Papadatos-Pastos D., Carnell D., Mendes R., George J., Navani N., 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., Idries F., Joseph L., Bishop P., Chaturved A., Quinn A.M., 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 D.G., Chemi F., Pierce J., Gulati S., Naidu B., Langman G., Trotter S., Bellamy M., Bancroft H., Kerr A., Kadiri S., Webb J., Middleton G., Djearaman M., Fennell D., Shaw J.A., Le Quesne J., Moore D., Nakas A., Rathinam S., Monteiro W., Marshall H., Nelson L., Bennett J., Riley J., Primrose L., Martinson L., Anand G., Khan S., Amadi A., Nicolson M., Kerr K., Palmer S., Remmen H., Miller J., Buchan K., Chetty M., Gomersall L., Lester J., Edwards A., Morgan F., Adams H., Davies H., Kornaszewska M., Attanoos R., Lock S., Verjee A., 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 M.T., Bowman A., Jordan S., Rice A., Raubenheimer H., Proli C., Cufari M.E., Ronquillo J.C., Kwayie A., Bhayani H., Hamilton M., Bakar Y., Mensah N., Ambrose L., Devaraj A., Buderi S., Finch J., Azcarate L., Chavan H., Green S., Mashinga H., Nicholson A.G., Lau K., Sheaff M., Schmid P., Conibear J., Ezhil V., Ismail B., Irvin-Sellers M., Prakash V., Russell P., Light T., Horey T., Danson S., Bury J., Edwards J., Hill J., Matthews S., Kitsanta Y., Suvarna K., Fisher P., Keerio A.D., Shackcloth M., Gosney J., Postmus P., Feeney S., Asante-Siaw J., Aerts HJWL, Dentro S., Dessimoz C.
ISSN
1097-4172 (Electronic)
ISSN-L
0092-8674
Publication state
Published
Issued date
30/11/2017
Peer-reviewed
Oui
Volume
171
Number
6
Pages
1259-1271.e11
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Abstract
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.
Keywords
Adult, Aged, Aged, 80 and over, Antigen Presentation, Carcinoma, Non-Small-Cell Lung/genetics, Carcinoma, Non-Small-Cell Lung/immunology, Carcinoma, Non-Small-Cell Lung/pathology, Carcinoma, Non-Small-Cell Lung/therapy, Cohort Studies, Female, HLA Antigens/genetics, HLA Antigens/immunology, Humans, Loss of Heterozygosity, Lung Neoplasms/genetics, Lung Neoplasms/immunology, Lung Neoplasms/pathology, Lung Neoplasms/therapy, Male, Middle Aged, Mutation, Polymorphism, Single Nucleotide, Tumor Escape, bioinformatics, cancer evolution, chromosomal instability, copy number, heterogeneity, immune-editing, immune-escape, loss of heterozygosity, lung cancer, neoantigen
Pubmed
Web of science
Publisher's website
Open Access
Yes
Create date
23/01/2020 15:29
Last modification date
30/04/2021 6:16
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