Skip to main content
SpringerLink
Log in

Inflammation and Head and Neck Squamous Cell Carcinoma

  • Chapter
  • First Online:
Book cover Molecular Determinants of Head and Neck Cancer

Part of the book series: Current Cancer Research ((CUCR))

  • 544 Accesses

Abstract

Inflammation is a process that is involved in several stages of development and malignant progression of head and neck squamous cell carcinoma. Tobacco and alcohol, human papillomaviruses (HPV), or Epstein-Barr viruses (EBV) can initiate and establish chronic inflammation through a variety of mechanisms. Genomic alterations or viral oncoproteins that induce signaling via phosphatidylinositol 3-kinase (PI3K) and transcription factor nuclear factor-kappaB (NF-κB) regulate numerous genes that promote survival of cancer cells, while they induce inflammatory myeloid-derived suppressor cell (MDSC) and T regulatory (Treg) cell responses that interfere with effector T-cell immunity. Molecular therapies targeting signaling in cancer cells and these deleterious inflammatory cells are being combined with new PD-L1/PD-1 and CTLA-4 immune checkpoint inhibitors to explore better ways to harness the immune system in control of cancer.

Supported by NIDCD Intramural Projects ZIA-DC-000016, 73 and 74.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Gasparoto TH, et al. Inflammatory events during murine squamous cell carcinoma development. J Inflamm (Lond). 2012;9(1):46.

    Article  CAS  Google Scholar 

  2. Choudhari SK, et al. Oxidative and antioxidative mechanisms in oral cancer and precancer: a review. Oral Oncol. 2014;50(1):10–8.

    Article  CAS  PubMed  Google Scholar 

  3. Hecht SS. Lung carcinogenesis by tobacco smoke. Int J Cancer. 2012;131(12):2724–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. West KA, et al. Tobacco carcinogen-induced cellular transformation increases Akt activation in vitro and in vivo. Chest. 2004;125(5 Suppl):101S–2S.

    Article  PubMed  Google Scholar 

  5. Tsurutani J, et al. Tobacco components stimulate Akt-dependent proliferation and NFkappaB-dependent survival in lung cancer cells. Carcinogenesis. 2005;26(7):1182–95.

    Article  CAS  PubMed  Google Scholar 

  6. Dennis PA, et al. The biology of tobacco and nicotine: bench to bedside. Cancer Epidemiol Biomark Prev. 2005;14(4):764–7.

    Article  CAS  Google Scholar 

  7. Miyamoto S. Nuclear initiated NF-kappaB signaling: NEMO and ATM take center stage. Cell Res. 2011;21(1):116–30.

    Article  CAS  PubMed  Google Scholar 

  8. Zu Y, et al. Lipopolysaccharide-induced toll-like receptor 4 signaling in esophageal squamous cell carcinoma promotes tumor proliferation and regulates inflammatory cytokines expression. Dis Esophagus. 2017;30(2):1–8.

    PubMed  Google Scholar 

  9. Farnebo L, et al. Targeting toll-like receptor 2 inhibits growth of head and neck squamous cell carcinoma. Oncotarget. 2015;6(12):9897–907.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Van Waes C. Nuclear factor-kappaB in development, prevention, and therapy of cancer. Clin Cancer Res. 2007;13(4):1076–82.

    Article  PubMed  Google Scholar 

  11. Cancer Genome Atlas N. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015;517(7536):576–82.

    Article  CAS  Google Scholar 

  12. Hutti JE, et al. Oncogenic PI3K mutations lead to NF-kappaB-dependent cytokine expression following growth factor deprivation. Cancer Res. 2012;72(13):3260–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Yang X, et al. DeltaNp63 versatilely regulates a broad NF-kappaB gene program and promotes squamous epithelial proliferation, migration, and inflammation. Cancer Res. 2011;71(10):3688–700.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lee TL, et al. A signal network involving coactivated NF-kappaB and STAT3 and altered p53 modulates BAX/BCL-XL expression and promotes cell survival of head and neck squamous cell carcinomas. Int J Cancer. 2008;122(9):1987–98.

    Article  CAS  PubMed  Google Scholar 

  15. Duan J, et al. Nuclear factor-kappaB p65 small interfering RNA or proteasome inhibitor bortezomib sensitizes head and neck squamous cell carcinomas to classic histone deacetylase inhibitors and novel histone deacetylase inhibitor PXD101. Mol Cancer Ther. 2007;6(1):37–50.

    Article  CAS  PubMed  Google Scholar 

  16. Duffey DC, et al. Expression of a dominant-negative mutant inhibitor-kappaBalpha of nuclear factor-kappaB in human head and neck squamous cell carcinoma inhibits survival, proinflammatory cytokine expression, and tumor growth in vivo. Cancer Res. 1999;59(14):3468–74.

    PubMed  CAS  Google Scholar 

  17. Bancroft CC, et al. Coexpression of proangiogenic factors IL-8 and VEGF by human head and neck squamous cell carcinoma involves coactivation by MEK-MAPK and IKK-NF-kappaB signal pathways. Clin Cancer Res. 2001;7(2):435–42.

    PubMed  CAS  Google Scholar 

  18. Loukinova E, et al. Expression of proangiogenic chemokine Gro 1 in low and high metastatic variants of pam murine squamous cell carcinoma is differentially regulated by IL-1alpha, EGF and TGF-beta1 through NF-kappaB dependent and independent mechanisms. Int J Cancer. 2001;94(5):637–44.

    Article  CAS  PubMed  Google Scholar 

  19. Loukinova E, et al. Growth regulated oncogene-alpha expression by murine squamous cell carcinoma promotes tumor growth, metastasis, leukocyte infiltration and angiogenesis by a host CXC receptor-2 dependent mechanism. Oncogene. 2000;19(31):3477–86.

    Article  CAS  PubMed  Google Scholar 

  20. Young MR, et al. Human squamous cell carcinomas of the head and neck chemoattract immune suppressive CD34(+) progenitor cells. Hum Immunol. 2001;62(4):332–41.

    Article  CAS  PubMed  Google Scholar 

  21. Pak AS, et al. Mechanisms of immune suppression in patients with head and neck cancer: presence of CD34(+) cells which suppress immune functions within cancers that secrete granulocyte-macrophage colony-stimulating factor. Clin Cancer Res. 1995;1(1):95–103.

    PubMed  CAS  Google Scholar 

  22. Sawanobori Y, et al. Chemokine-mediated rapid turnover of myeloid-derived suppressor cells in tumor-bearing mice. Blood. 2008;111(12):5457–66.

    Article  CAS  PubMed  Google Scholar 

  23. Youn JI, et al. Subsets of myeloid-derived suppressor cells in tumor-bearing mice. J Immunol. 2008;181(8):5791–802.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Sakaguchi S, et al. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol. 1995;155(3):1151–64.

    PubMed  CAS  Google Scholar 

  25. Bluestone JA, Abbas AK. Natural versus adaptive regulatory T cells. Nat Rev Immunol. 2003;3(3):253–7.

    Article  CAS  PubMed  Google Scholar 

  26. Beyer M, Schultze JL. Regulatory T cells in cancer. Blood. 2006;108(3):804–11.

    Article  CAS  PubMed  Google Scholar 

  27. Tartour E, et al. Serum soluble interleukin-2 receptor concentrations as an independent prognostic marker in head and neck cancer. Lancet. 2001;357(9264):1263–4.

    Article  CAS  PubMed  Google Scholar 

  28. Kumar V, et al. The nature of myeloid-derived suppressor cells in the tumor microenvironment. Trends Immunol. 2016;37(3):208–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Rodriguez PC, et al. Regulation of T cell receptor CD3zeta chain expression by L-arginine. J Biol Chem. 2002;277(24):21123–9.

    Article  CAS  PubMed  Google Scholar 

  30. Mazzoni A, et al. Myeloid suppressor lines inhibit T cell responses by an NO-dependent mechanism. J Immunol. 2002;168(2):689–95.

    Article  CAS  PubMed  Google Scholar 

  31. Schindler H, Bogdan C. NO as a signaling molecule: effects on kinases. Int Immunopharmacol. 2001;1(8):1443–55.

    Article  CAS  PubMed  Google Scholar 

  32. Lee GK, et al. Tryptophan deprivation sensitizes activated T cells to apoptosis prior to cell division. Immunology. 2002;107(4):452–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Huang B, et al. Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host. Cancer Res. 2006;66(2):1123–31.

    Article  CAS  PubMed  Google Scholar 

  34. Huang B, et al. CCL2/CCR2 pathway mediates recruitment of myeloid suppressor cells to cancers. Cancer Lett. 2007;252(1):86–92.

    Article  CAS  Google Scholar 

  35. Youn JI, et al. Epigenetic silencing of retinoblastoma gene regulates pathologic differentiation of myeloid cells in cancer. Nat Immunol. 2013;14(3):211–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Chikamatsu K, et al. Immunosuppressive activity of CD14+ HLA-DR- cells in squamous cell carcinoma of the head and neck. Cancer Sci. 2012;103(6):976–83.

    Article  CAS  PubMed  Google Scholar 

  37. Chen WC, et al. Inflammation-induced myeloid-derived suppressor cells associated with squamous cell carcinoma of the head and neck. Head Neck. 2017;39(2):347–55.

    Article  PubMed  Google Scholar 

  38. Corzo CA, et al. HIF-1alpha regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment. J Exp Med. 2010;207(11):2439–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Clavijo PE, et al. Resistance to CTLA-4 checkpoint inhibition reversed through selective elimination of granulocytic myeloid cells. Oncotarget. 2017;8(34):55804–20.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Chen Z, et al. Expression of proinflammatory and proangiogenic cytokines in patients with head and neck cancer. Clin Cancer Res. 1999;5(6):1369–79.

    PubMed  CAS  Google Scholar 

  41. Califano JA, et al. Tadalafil augments tumor specific immunity in patients with head and neck squamous cell carcinoma. Clin Cancer Res. 2015;21(1):30–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Weed DT, et al. Tadalafil reduces myeloid-derived suppressor cells and regulatory T cells and promotes tumor immunity in patients with head and neck squamous cell carcinoma. Clin Cancer Res. 2015;21(1):39–48.

    Article  CAS  PubMed  Google Scholar 

  43. Davis RJ, et al. Anti-PD-L1 efficacy can be enhanced by inhibition of myeloid-derived suppressor cells with a selective inhibitor of PI3Kdelta/gamma. Cancer Res. 2017;77(10):2607–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Ondondo B, et al. Home sweet home: the tumor microenvironment as a haven for regulatory T cells. Front Immunol. 2013;4:197.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Chaudhary B, Elkord E. Regulatory T cells in the tumor microenvironment and Cancer progression: role and therapeutic targeting. Vaccines (Basel). 2016;4(3): pii, E28.

    Google Scholar 

  46. Chikamatsu K, et al. Relationships between regulatory T cells and CD8+ effector populations in patients with squamous cell carcinoma of the head and neck. Head Neck. 2007;29(2):120–7.

    Article  PubMed  Google Scholar 

  47. Schaefer C, et al. Characteristics of CD4+CD25+ regulatory T cells in the peripheral circulation of patients with head and neck cancer. Br J Cancer. 2005;92(5):913–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Lau KM, et al. Increase in circulating Foxp3+CD4+CD25(high) regulatory T cells in nasopharyngeal carcinoma patients. Br J Cancer. 2007;96(4):617–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Jie HB, et al. Intratumoral regulatory T cells upregulate immunosuppressive molecules in head and neck cancer patients. Br J Cancer. 2013;109(10):2629–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Shang B, et al. Prognostic value of tumor-infiltrating FoxP3+ regulatory T cells in cancers: a systematic review and meta-analysis. Sci Rep. 2015;5:15179.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Venet F, et al. Human CD4+CD25+ regulatory T lymphocytes inhibit lipopolysaccharide-induced monocyte survival through a Fas/Fas ligand-dependent mechanism. J Immunol. 2006;177(9):6540–7.

    Article  CAS  PubMed  Google Scholar 

  52. Ali K, et al. Inactivation of PI(3)K p110delta breaks regulatory T-cell-mediated immune tolerance to cancer. Nature. 2014;510(7505):407–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Wing K, et al. CTLA-4 control over Foxp3+ regulatory T cell function. Science. 2008;322(5899):271–5.

    Article  CAS  PubMed  Google Scholar 

  54. Parry RV, et al. CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol Cell Biol. 2005;25(21):9543–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Peggs KS, et al. Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies. J Exp Med. 2009;206(8):1717–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Tarhini AA, et al. Differing patterns of circulating regulatory T cells and myeloid-derived suppressor cells in metastatic melanoma patients receiving anti-CTLA4 antibody and interferon-alpha or TLR-9 agonist and GM-CSF with peptide vaccination. J Immunother. 2012;35(9):702–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Wang W, et al. PD1 blockade reverses the suppression of melanoma antigen-specific CTL by CD4+ CD25(hi) regulatory T cells. Int Immunol. 2009;21(9):1065–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Schuler PJ, et al. Effects of adjuvant chemoradiotherapy on the frequency and function of regulatory T cells in patients with head and neck cancer. Clin Cancer Res. 2013;19(23):6585–96.

    Article  CAS  PubMed  Google Scholar 

  59. Vander Broek R, et al. The PI3K/Akt/mTOR axis in head and neck cancer: functions, aberrations, cross-talk, and therapies. Oral Dis. 2015;21(7):815–25.

    Article  CAS  PubMed  Google Scholar 

  60. Taube JM, et al. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med. 2012;4(127):127ra37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Keck MK, et al. Integrative analysis of head and neck cancer identifies two biologically distinct HPV and three non-HPV subtypes. Clin Cancer Res. 2015;21(4):870–81.

    Article  CAS  PubMed  Google Scholar 

  62. Ferris RL, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375(19):1856–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Seiwert TY, 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(7):956–65.

    Article  CAS  PubMed  Google Scholar 

  64. Woo SR, Corrales L, Gajewski TF. Innate immune recognition of cancer. Annu Rev Immunol. 2015;33:445–74.

    Article  CAS  PubMed  Google Scholar 

  65. Corrales L, et al. The host STING pathway at the interface of cancer and immunity. J Clin Invest. 2016;126(7):2404–11.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Moore E, et al. Established T cell-inflamed tumors rejected after adaptive resistance was reversed by combination STING activation and PD-1 pathway blockade. Cancer Immunol Res. 2016;4(12):1061–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Gadkaree SK, et al. Induction of tumor regression by intratumoral STING agonists combined with anti-programmed death-L1 blocking antibody in a preclinical squamous cell carcinoma model. Head Neck. 2017;39(6):1086–94.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA

    Paul E. Clavijo, Clint T. Allen, Nicole C. Schmitt & Carter Van Waes

Authors
  1. Paul E. Clavijo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Clint T. Allen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nicole C. Schmitt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Carter Van Waes
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carter Van Waes .

Editor information

Editors and Affiliations

  1. Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA

    Barbara Burtness

  2. Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA

    Erica A. Golemis

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Clavijo, P.E., Allen, C.T., Schmitt, N.C., Van Waes, C. (2018). Inflammation and Head and Neck Squamous Cell Carcinoma. In: Burtness, B., Golemis, E. (eds) Molecular Determinants of Head and Neck Cancer. Current Cancer Research. Humana Press, Cham. https://doi.org/10.1007/978-3-319-78762-6_13

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-78762-6_13

  • Published:

  • Publisher Name: Humana Press, Cham

  • Print ISBN: 978-3-319-78761-9

  • Online ISBN: 978-3-319-78762-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation