气候变化领域集成服务门户(CCPortal): Immune evasion in HPV-head and neck precancer-cancer transition is driven by an aneuploid switch involving chromosome 9p loss

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DOI	10.1073/pnas.2022655118
	Immune evasion in HPV-head and neck precancer-cancer transition is driven by an aneuploid switch involving chromosome 9p loss
	William W.N.; Jr.; Zhao X.; Bianchi J.J.; Lin H.Y.; Cheng P.; Lee J.J.; Carter H.; Alexandrov L.B.; Abraham J.P.; Spetzler D.B.; Dubinett S.M.; Cleveland D.W.; Cavenee W.; Davoli T.; Lippman S.M.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:19
英文摘要	An aneuploid-immune paradox encompasses somatic copy-number alterations (SCNAs), unleashing a cytotoxic response in experimental precancer systems, while conversely being associated with immune suppression and cytotoxic-cell depletion in human tumors, especially head and neck cancer (HNSC). We present evidence from patient samples and cell lines that alterations in chromosome dosage contribute to an immune hot-to-cold switch during human papillomavirus-negative (HPV.) head and neck tumorigenesis. Overall SCNA (aneuploidy) level was associated with increased CD3+and CD8+T cell microenvironments in precancer (mostly CD3+, linked to trisomy and aneuploidy), but with T cell-deficient tumors. Early lesions with 9p21.3 loss were associated with depletion of cytotoxic T cell infiltration in TP53 mutant tumors; and with aneuploidy were associatedwith increased NK-cell infiltration. The strongest driver of cytotoxic T cell and Immune Score depletion in oral cancer was 9parm level loss, promoting profound decreases of pivotal IFN-γ-related chemokines (e.g., CXCL9) and pathway genes. Chromosome 9p21.3 deletion contributed mainly to cell-intrinsic senescence suppression, but deletion of the entire arm was necessary to diminish levels of cytokine, JAK-STAT, and Hallmark NF-κB pathways. Finally, 9p arm-level loss and JAK2-PD-L1 codeletion (at 9p24) were predictive markers of poor survival in recurrent HPV-HNSC after anti-PD- 1 therapy; likely amplified by independent aneuploidy-induced immune-cold microenvironments observed here. We hypothesize that 9p21.3 arm-loss expansion and epistatic interactions allow oral precancer cells to acquire properties to overcome a proimmunogenic aneuploid checkpoint, transform and invade. These findings enable distinct HNSC interception and precision-therapeutic approaches, concepts that may apply to other CN-driven neoplastic, immune or aneuploid diseases, and immunotherapies. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Aneuploidy; Genomic copy number variation; Head and neck cancer; Immunotherapy; Premalignancy
语种	英语
scopus关键词	CXCL9 chemokine; gamma interferon; Janus kinase 2; nivolumab; pembrolizumab; programmed death 1 ligand 1; CD274 protein, human; CD3 antigen; cytokine; JAK2 protein, human; Janus kinase 2; programmed death 1 ligand 1; adult; aged; Article; cancer immunotherapy; cancer recurrence; cancer survival; carcinogenesis; CD3+ T lymphocyte; CD8+ T lymphocyte; cell aging; chromosome 9p; chromosome deletion; chromosome loss; cohort analysis; controlled study; copy number variation; cytotoxic T lymphocyte; epistasis; head and neck cancer; human; human cell; human tissue; immune evasion; JAK-STAT signaling; lymphocytic infiltration; major clinical study; malignant transformation; mouth cancer; natural killer cell; NF kB signaling; precancer; prediction; priority journal; T cell depletion; trisomy; tumor microenvironment; tumor suppressor gene; Wart virus; aneuploidy; chromosome; chromosome deletion; gene expression regulation; genetics; head and neck tumor; immunotherapy; middle aged; papillomavirus infection; tumor cell line; very elderly; young adult; Adult; Aged; Aged, 80 and over; Aneuploidy; B7-H1 Antigen; CD3 Complex; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Chromosome Deletion; Chromosomes; Cytokines; DNA Copy Number Variations; Gene Expression Regulation, Neoplastic; Genes, p53; Head and Neck Neoplasms; Humans; Immune Evasion; Immunotherapy; Janus Kinase 2; Middle Aged; Papillomavirus Infections; T-Lymphocytes, Cytotoxic; Tumor Microenvironment; Young Adult
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251188
作者单位	Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States; Hospital BP, A Beneficencia Portuguesa de Sao Paulo, Sao Paulo, 01323-001, Brazil; Department of Biochemistry and Molecular Pharmacology, Institute for Systems Genetics, New York University Langone Health, New York, NY 10016, United States; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States; Moores Cancer Center, University of California San Diego, San Diego, CA 92037, United States; Department of Medicine, University of California San Diego, San Diego, CA 92037, United States; Department of Cellular and Molecular Medicine, University of California San Diego, San Diego, CA 92037, United States; Department of Bioengineering, University of California San Diego, San Diego, CA 92037, United States; Research and Development, Caris Life Sciences, Irving, TX 75039, United States; Jonsson Comprehensive Canc...
推荐引用方式 GB/T 7714	William W.N.,Jr.,Zhao X.,et al. Immune evasion in HPV-head and neck precancer-cancer transition is driven by an aneuploid switch involving chromosome 9p loss[J],2021,118(19).
APA	William W.N..,Jr..,Zhao X..,Bianchi J.J..,Lin H.Y..,...&Lippman S.M..(2021).Immune evasion in HPV-head and neck precancer-cancer transition is driven by an aneuploid switch involving chromosome 9p loss.Proceedings of the National Academy of Sciences of the United States of America,118(19).
MLA	William W.N.,et al."Immune evasion in HPV-head and neck precancer-cancer transition is driven by an aneuploid switch involving chromosome 9p loss".Proceedings of the National Academy of Sciences of the United States of America 118.19(2021).