Distinct immune evasion in APOBEC-enriched, HPV-negative HNSCC.
APOBEC Deaminases
/ genetics
Biomarkers, Tumor
/ genetics
Cohort Studies
Exome
/ genetics
Female
Gene Expression Regulation, Neoplastic
/ genetics
Head and Neck Neoplasms
/ immunology
Humans
Immune Evasion
/ genetics
Inflammation
/ genetics
Male
Middle Aged
Mutation
/ genetics
Papillomaviridae
/ immunology
Papillomavirus Infections
/ genetics
Sequence Analysis, RNA
/ methods
Squamous Cell Carcinoma of Head and Neck
/ genetics
T-Lymphocytes
/ immunology
Transcriptome
/ genetics
APOBEC
head and neck cancer
immune checkpoint inhibition
mutational signature
tumor inflammation
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
15 10 2020
15 10 2020
Historique:
received:
21
10
2019
revised:
06
04
2020
accepted:
11
05
2020
pubmed:
30
5
2020
medline:
13
4
2021
entrez:
30
5
2020
Statut:
ppublish
Résumé
Immune checkpoint inhibition leads to response in some patients with head and neck squamous cell carcinoma (HNSCC). Robust biomarkers are lacking to date. We analyzed viral status, gene expression signatures, mutational load and mutational signatures in whole exome and RNA-sequencing data of the HNSCC TCGA dataset (n = 496) and a validation set (DKTK MASTER cohort, n = 10). Public single-cell gene expression data from 17 HPV-negative HNSCC were separately reanalyzed. APOBEC3-associated TCW motif mutations but not total single nucleotide variant burden were significantly associated with inflammation. This association was restricted to HPV-negative HNSCC samples. An APOBEC-enriched, HPV-negative subgroup was identified, that showed higher T-cell inflammation and immune checkpoint expression, as well as expression of APOBEC3 genes. Mutations in immune-evasion pathways were also enriched in these tumors. Analysis of single-cell sequencing data identified expression of APOBEC3B and 3C genes in malignant cells. We identified an APOBEC-enriched subgroup of HPV-negative HNSCC with a distinct immunogenic phenotype, potentially mediating response to immunotherapy.
Substances chimiques
Biomarkers, Tumor
0
APOBEC Deaminases
EC 3.5.4.5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2293-2302Informations de copyright
© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
Références
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646-674.
Ferris RL, Blumenschein G, Fayette J, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375:1856-1867.
Seiwert TY, Burtness B, Mehra R, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Lancet Oncol. 2016;17:956-965.
Ayers M, Lunceford J, Nebozhyn M, et al. IFN-γ-related mRNA profile predicts clinical response to PD-1 blockade. J Clin Invest. 2017;127:2930-2940.
van Allen EM, Miao D, Schilling B, et al. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science (80- ). 2015;350:207-211.
Cristescu R, Mogg R, Ayers M, et al. Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy. Science (80- ). 2018;362:eaar3593.
Rieke DT, Klinghammer K, Keilholz U. Targeted therapy of head and neck cancer. Oncol Res Treat. 2016;39:780-786.
Keck MK, Zuo Z, Khattri A, et al. Integrative analysis of head and neck cancer identifies two biologically distinct HPV and three non-HPV subtypes. Clin Cancer Res. 2015;21:870-881.
Mehra R, Seiwert TY, Gupta S, et al. Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long-term follow-up in KEYNOTE-012. Br J Cancer. 2018;119:153-159.
Blank CU, Haanen JB, Ribas A, Schumacher TN. The cancer immunogram. Science (80-). 2016;352:658-660.
Henderson S, Chakravarthy A, Su X, Boshoff C, Fenton TR. APOBEC-mediated cytosine deamination links PIK3CA helical domain mutations to human papillomavirus-driven tumor development. Cell Rep. 2014;7(6):1833-1841. https://doi.org/10.1016/j.celrep.2014.05.012
Venkatesan S, Rosenthal R, Kanu N, et al. Perspective: APOBEC mutagenesis in drug resistance and immune escape in HIV and cancer evolution. Ann Oncol. 2018;29:563-572.
Burns MB, Temiz NA, Harris RS. Evidence for APOBEC3B mutagenesis in multiple human cancers. Nat Genet. 2013;45:977-983.
Alexandrov LB, Nik-Zainal S, Wedge DC, et al. Signatures of mutational processes in human cancer. Nature. 2013;500:415-421.
Lawrence MS, Sougnez C, Lichtenstein L, et al. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015;517:576-582.
Collisson EA, Campbell JD, Brooks AN, et al. Comprehensive molecular profiling of lung adenocarcinoma. Nature. 2014;511:543-550.
Weinstein JN, Akbani R, Broom BM, et al. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature. 2014;507(7492):315-322. https://doi.org/10.1038/nature12965
Hammerman PS, Voet D, Lawrence MS, et al. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012;489:519-525.
Roberts SA, Lawrence MS, Klimczak LJ, et al. An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers. Nat Genet. 2013;45:970-976.
Huang PJ, Chiu LY, Lee CC, et al. MSignatureDB: a database for deciphering mutational signatures in human cancers. Nucleic Acids Res. 2018;46(D1):D964-D970. https://doi.org/10.1093/nar/gkx1133
Buitrago-Pérez A, Garaulet G, Vázquez-Carballo A, Paramio JM, García-Escudero R. Molecular signature of HPV-induced carcinogenesis: pRb, p53 and gene expression profiling. Curr Genomics. 2009;10:26-34.
Tang K-W, Alaei-Mahabadi B, Samuelsson T, Lindh M, Larsson E. The landscape of viral expression and host gene fusion and adaptation in human cancer. Nat Commun. 2013;4:2513.
Gao J, Aksoy BA, Dogrusoz U, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013;6:pl1-pl1.
Charoentong P, Finotello F, Angelova M, et al. Pan-cancer Immunogenomic analyses reveal genotype-Immunophenotype relationships and predictors of response to checkpoint blockade. Cell Rep. 2017;18:248-262.
Hänzelmann S, Castelo R, Guinney J. GSVA: gene set variation analysis for microarray and RNA-Seq data. BMC Bioinformatics. 2013;14:7. https://doi.org/10.1186/1471-2105-14-7
Ritchie ME, Phipson B, Wu D, et al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47. https://doi.org/10.1093/nar/gkv007
Patel SJ, Sanjana NE, Kishton RJ, et al. Identification of essential genes for cancer immunotherapy. Nature. 2017;548:537-542.
Jäger M, Wang K, Bauer S, Smedley D, Krawitz P, Robinson PN. Jannovar: a Java library for exome annotation. Hum Mutat. 2014;35:548-555.
Storey J. qvalue: Q-Value estimation for false discovery rate control. R package version 2.0.0. 2015. DOI: https://doi.org/10.18129/B9.bioc.qvalue
Puram SV, Tirosh I, Parikh AS, et al. Single-cell transcriptomic analysis of primary and metastatic tumor ecosystems in head and neck cancer. Cell. 2017;171:1611-1624.e24.
Butler A, Hoffman P, Smibert P, Papalexi E, Satija R. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat Biotechnol. 2018;36:411-420.
Patro R, Duggal G, Love MI, Irizarry RA, Kingsford C. Salmon provides fast and bias-aware quantification of transcript expression. Nat Methods. 2017;14:417-419.
Chow LQM, Mehra R, Haddad RI, et al. Biomarkers and response to pembrolizumab (pembro) in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). J Clin Oncol. 2016;34:6010-6010.
McGranahan N, Favero F, de Bruin EC, Birkbak NJ, Szallasi Z, Swanton C. Clonal status of actionable driver events and the timing of mutational processes in cancer evolution. Sci Transl Med. 2015;7:283ra54.
Burtness B, Harrington KJ, , , et al. KEYNOTE-048: phase III study of first-line pembrolizumab (P) for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Ann Oncol. 2018;29(Suppl. 8):viii729-viii729. https://doi.org/10.1093/annonc/mdy424.045
Budczies J, Seidel A, Christopoulos P, et al. Integrated analysis of the immunological and genetic status in and across cancer types: impact of mutational signatures beyond tumor mutational burden. Oncoimmunology. 2018;7:e1526613. https://doi.org/10.1080/2162402X.2018.1526613
Wang S, Jia M, He Z, Liu X-S. APOBEC3B and APOBEC mutational signature as potential predictive markers for immunotherapy response in non-small cell lung cancer. Oncogene. 2018;37:3924-3936.
Faden DL, Ding F, Lin Y, et al. APOBEC mutagenesis is tightly linked to the immune landscape and immunotherapy biomarkers in head and neck squamous cell carcinoma. Oral Oncol. 2019;96:140-147.
Swanton C, McGranahan N, Starrett GJ, Harris RS. APOBEC enzymes: mutagenic fuel for cancer evolution and heterogeneity. Cancer Discov. 2015;5:704-712.
Chen J, Miller BF, Furano AV. Repair of naturally occurring mismatches can induce mutations in flanking DNA. Elife. 2014;3:e02001. https://doi.org/10.7554/eLife.02001
Taylor BJ, Nik-Zainal S, Wu YL, et al. DNA deaminases induce break-associated mutation showers with implication of APOBEC3B and 3A in breast cancer kataegis. Elife. 2013;2:e00534. https://doi.org/10.7554/eLife.00534
Foy J-P, Bertolus C, Michallet M-C, et al. The immune microenvironment of HPV-negative oral squamous cell carcinoma from never-smokers and never-drinkers patients suggests higher clinical benefit of IDO1 and PD1/PD-L1 blockade. Ann Oncol. 2017;28:1934-1941.
Leonard B, Starrett GJ, Maurer MJ, et al. APOBEC3G expression correlates with T-cell infiltration and improved clinical outcomes in high-grade serous ovarian carcinoma. Clin Cancer Res. 2016;22:4746-4755.
Petljak M, Alexandrov LB, Brammeld JS, et al. Characterizing mutational signatures in human cancer cell lines reveals episodic APOBEC mutagenesis. Cell. 2019;176:1282-1294.e20. https://doi.org/10.1016/j.cell.2019.02.012
Mullane SA, Werner L, Rosenberg J, et al. Correlation of Apobec Mrna expression with overall survival and pd-l1 expression in urothelial carcinoma. Sci Rep. 2016;6:27702.
Glaser AP, Fantini D, Wang Y, et al. APOBEC-mediated mutagenesis in urothelial carcinoma is associated with improved survival, mutations in DNA damage response genes, and immune response. Oncotarget. 2018;9:4537-4548.
Miao D, Margolis CA, Vokes NI, et al. Genomic correlates of response to immune checkpoint blockade in microsatellite-stable solid tumors. Nat Genet. 2018;50:1271-1281.