Journal Article
. 2018 Feb; 96:28-36.
doi: 10.1016/j.molimm.2018.02.005.

Immunological network analysis in HPV associated head and neck squamous cancer and implications for disease prognosis

Xiaohang Chen 1 Bingqing Yan 1 Huihuang Lou 1 Zhenji Shen 1 Fangjia Tong 1 Aixia Zhai 2 Lanlan Wei 3 Fengmin Zhang 4 
Affiliations
  • PMID: 29477933
  •     28 citations

Abstract

Human papillomavirus-positive (HPV+) head and neck squamous cell cancer (HNSCC) exhibits a better prognosis than HPV-negative (HPV-) HNSCC. This difference may in part be due to enhanced immune activation in the HPV+ HNSCC tumor microenvironment. To characterize differences in immune activation between HPV+ and HPV- HNSCC tumors, we identified and annotated differentially expressed genes based upon mRNA expression data from The Cancer Genome Atlas (TCGA). Immune network between immune cells and cytokines was constructed by using single sample Gene Set Enrichment Analysis and conditional mutual information. Multivariate Cox regression analysis was used to determine the prognostic value of immune microenvironment characterization. A total of 1673 differentially expressed genes were functionally annotated. We found that genes upregulated in HPV+ HNSCC are enriched in immune-associated processes. And the up-regulated gene sets were validated by Gene Set Enrichment Analysis. The microenvironment of HPV+ HNSCC exhibited greater numbers of infiltrating B and T cells and fewer neutrophils than HPV- HNSCC. These findings were validated by two independent datasets in the Gene Expression Omnibus (GEO) database. Further analyses of T cell subtypes revealed that cytotoxic T cell subtypes predominated in HPV+ HNSCC. In addition, the ratio of M1/M2 macrophages was much higher in HPV+ HNSCC. The infiltration of these immune cells was correlated with differentially expressed cytokine-associated genes. Enhanced infiltration of B cells and CD8+ T cells were identified as independent protective factors, while high neutrophil infiltration was a risk enhancing factor for HPV+ HNSCC patients. A schematic model of immunological network was established for HPV+ HNSCC to summarize our findings.

Keywords: Bioinformatics; HPV; Head and neck cancer; Immunological network.

Treatment-naïve HPV+ head and neck cancers display a T-cell-inflamed phenotype distinct from their HPV- counterparts that has implications for immunotherapy.
Steven F Gameiro, Farhad Ghasemi, +4 authors, Saman Maleki Vareki.
Oncoimmunology, 2018 Oct 06; 7(10). PMID: 30288365    Free PMC article.
Utility of CD8 score by automated quantitative image analysis in head and neck squamous cell carcinoma.
Douglas J Hartman, Fahad Ahmad, +2 authors, Liron Pantanowitz.
Oral Oncol, 2018 Nov 10; 86. PMID: 30409313    Free PMC article.
Enhanced Radiation Sensitivity of Human Papillomavirus-Driven Head and Neck Cancer: Focus on Immunological Aspects.
Mine Özcan-Wahlbrink, Christoph Schifflers, Angelika B Riemer.
Front Immunol, 2019 Dec 19; 10. PMID: 31849993    Free PMC article.
Review.
Transcriptomics and Epigenomics in head and neck cancer: available repositories and molecular signatures.
Mara S Serafini, Laura Lopez-Perez, +3 authors, Carlo Resteghini.
Cancers Head Neck, 2020 Jan 29; 5. PMID: 31988797    Free PMC article.
Review.
The Double-Edged Sword-How Human Papillomaviruses Interact With Immunity in Head and Neck Cancer.
Hao-Fan Wang, Sha-Sha Wang, +4 authors, Xin-Hua Liang.
Front Immunol, 2019 Apr 20; 10. PMID: 31001266    Free PMC article.
Review.
Interplay between cancer cells and M2 macrophages is necessary for miR-550a-3-5p down-regulation-mediated HPV-positive OSCC progression.
Ming-Xin Cao, Wei-Long Zhang, +9 authors, Ya-Ling Tang.
J Exp Clin Cancer Res, 2020 Jun 05; 39(1). PMID: 32493454    Free PMC article.
The Immune Microenvironment in Head and Neck Squamous Cell Carcinoma: on Subsets and Subsites.
Niels E Wondergem, Irene H Nauta, +2 authors, Rieneke van de Ven.
Curr Oncol Rep, 2020 Jul 01; 22(8). PMID: 32602047    Free PMC article.
Review.
M2 macrophages reduce the radiosensitivity of head and neck cancer by releasing HB‑EGF.
Enhui Fu, Tianyang Liu, +11 authors, Lanlan Wei.
Oncol Rep, 2020 Jul 07; 44(2). PMID: 32627036    Free PMC article.
Neutrophils infiltration and its correlation with human papillomavirus status in the oral squamous cell carcinoma.
Chen Li, Lei Zhao, +8 authors, Xun Qu.
Cancer Manag Res, 2019 Jun 27; 11. PMID: 31239772    Free PMC article.
The Host-Microbe Interplay in Human Papillomavirus-Induced Carcinogenesis.
Rei Wakabayashi, Yusuke Nakahama, Viet Nguyen, J Luis Espinoza.
Microorganisms, 2019 Jul 25; 7(7). PMID: 31337018    Free PMC article.
Review.
High Level Expression of MHC-II in HPV+ Head and Neck Cancers Suggests that Tumor Epithelial Cells Serve an Important Role as Accessory Antigen Presenting Cells.
Steven F Gameiro, Farhad Ghasemi, +2 authors, Joe S Mymryk.
Cancers (Basel), 2019 Aug 10; 11(8). PMID: 31394808    Free PMC article.
Immunological Network in Head and Neck Squamous Cell Carcinoma-A Prognostic Tool Beyond HPV Status.
Anna Fialová, Vladimír Koucký, +2 authors, Radek Špíšek.
Front Oncol, 2020 Oct 13; 10. PMID: 33042814    Free PMC article.
Review.
Identifying predictors of HPV-related head and neck squamous cell carcinoma progression and survival through patient-derived models.
Nicole D Facompre, Pavithra Rajagopalan, +17 authors, Devraj Basu.
Int J Cancer, 2020 Jun 02; 147(11). PMID: 32478869    Free PMC article.
Immune Escape Mechanisms and Their Clinical Relevance in Head and Neck Squamous Cell Carcinoma.
Barbara Seliger, Chiara Massa, +4 authors, Claudia Wickenhauser.
Int J Mol Sci, 2020 Sep 30; 21(19). PMID: 32987799    Free PMC article.
Review.
PRINS lncRNA Is a New Biomarker Candidate for HPV Infection and Prognosis of Head and Neck Squamous Cell Carcinomas.
Magda Kopczyńska, Tomasz Kolenda, +6 authors, Katarzyna Lamperska.
Diagnostics (Basel), 2020 Oct 02; 10(10). PMID: 32998396    Free PMC article.
Human Papillomavirus Infection in Head and Neck Squamous Cell Carcinomas: Transcriptional Triggers and Changed Disease Patterns.
Nikita Aggarwal, Joni Yadav, +9 authors, Alok C Bharti.
Front Cell Infect Microbiol, 2020 Dec 22; 10. PMID: 33344262    Free PMC article.
Review.
Tumor microenvironment: an evil nexus promoting aggressive head and neck squamous cell carcinoma and avenue for targeted therapy.
Ajaz A Bhat, Parvaiz Yousuf, +9 authors, Muzafar A Macha.
Signal Transduct Target Ther, 2021 Jan 14; 6(1). PMID: 33436555    Free PMC article.
Myeloid cell-targeted STAT3 inhibition sensitizes head and neck cancers to radiotherapy and T cell-mediated immunity.
Dayson Moreira, Sagus Sampath, +8 authors, Marcin Kortylewski.
J Clin Invest, 2020 Nov 25; 131(2). PMID: 33232304    Free PMC article.
Identification of Immune-Related Prognostic Biomarkers Associated with HPV-Positive Head and Neck Squamous Cell Carcinoma.
Yifei Chen, Jin Nie, +4 authors, Guilin Song.
J Immunol Res, 2021 Jan 29; 2021. PMID: 33506058    Free PMC article.
Characteristics of B lymphocyte infiltration in HPV+ head and neck squamous cell carcinoma.
Siwei Zhang, Bozhi Wang, +7 authors, Lanlan Wei.
Cancer Sci, 2021 Feb 03; 112(4). PMID: 33529452    Free PMC article.
High SEC61G expression predicts poor prognosis in patients with Head and Neck Squamous Cell Carcinomas.
Leifeng Liang, Qingwen Huang, +6 authors, Kai Hu.
J Cancer, 2021 Jun 08; 12(13). PMID: 34093796    Free PMC article.
Distinct Patterns of Myeloid Cell Infiltration in Patients With hrHPV-Positive and hrHPV-Negative Penile Squamous Cell Carcinoma: The Importance of Assessing Myeloid Cell Densities Within the Spatial Context of the Tumor.
Tynisha S Rafael, Hielke M de Vries, +8 authors, Oscar R Brouwer.
Front Immunol, 2021 Jul 02; 12. PMID: 34194435    Free PMC article.
Precision Medicine Gains Momentum: Novel 3D Models and Stem Cell-Based Approaches in Head and Neck Cancer.
Annette Affolter, Anne Lammert, +2 authors, Nicole Rotter.
Front Cell Dev Biol, 2021 Jul 27; 9. PMID: 34307351    Free PMC article.
Review.
Phytochemicals as Potential Chemopreventive and Chemotherapeutic Agents for Emerging Human Papillomavirus-Driven Head and Neck Cancer: Current Evidence and Future Prospects.
Nikita Aggarwal, Joni Yadav, +7 authors, Alok Chandra Bharti.
Front Pharmacol, 2021 Aug 07; 12. PMID: 34354591    Free PMC article.
Review.
Rapid Serial Immunoprofiling of the Tumor Immune Microenvironment by Fine Needle Sampling.
Juhyun Oh, Jonathan C T Carlson, +7 authors, Ralph Weissleder.
Clin Cancer Res, 2021 Jul 09; 27(17). PMID: 34233961    Free PMC article.
Immunotherapy in Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck.
Ronan W Hsieh, Steven Borson, Anastasia Tsagianni, Dan P Zandberg.
Front Oncol, 2021 Sep 21; 11. PMID: 34540672    Free PMC article.
Review.
DOCK8 Serves as a Prognostic Biomarker and Is Related to Immune Infiltration in Patients With HPV Positive Head and Neck Squamous Cell Carcinoma.
Zeying Zhang, Yandong Bao, +3 authors, Changfu Sun.
Cancer Control, 2021 Apr 30; 28. PMID: 33910393    Free PMC article.
The Key Differences between Human Papillomavirus-Positive and -Negative Head and Neck Cancers: Biological and Clinical Implications.
Steven F Powell, Lexi Vu, William C Spanos, Dohun Pyeon.
Cancers (Basel), 2021 Oct 24; 13(20). PMID: 34680354    Free PMC article.
Review.