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Adv Exp Med Biol. 2020;1296:79-101. doi: 10.1007/978-3-030-59038-3_5.

Laryngeal Tumor Microenvironment.

Advances in experimental medicine and biology

Georgia Karpathiou, Jean Marc Dumollard, Michel Peoc'h

Affiliations

  1. Pathology Department, North Hospital, University Hospital of Saint-Etienne, Saint-Priest-en-Jarez, France.

PMID: 34185287 DOI: 10.1007/978-3-030-59038-3_5

Abstract

Tumor microenvironment has been extensively studied in various forms of cancer, like head and neck squamous cell carcinoma. Progress in the field revealed the prognostic significance of the various components of the tumor's ecosystem and led to changes in treatment strategies, like including immunotherapy as an important tool. In this chapter, the microenvironment of tumors with a special interest in laryngeal cancer will be described. The issues assessed include innate immune response factors, like neutrophils, neutrophil extracellular traps (NET), platelets, macrophages M1 or M2, dendritic cells, natural killer cells, as well as adaptive immunity aspects, like cytotoxic, exhausted and regulatory T cells, and immune checkpoints (PD-1/PD-L1, CTLA4). Also, stroma-associated factors, like fibroblasts, fibrosis, extracellular matrix, vessels and perineural invasion, hypoxia and cancer metabolism aspects, as well as the pre-metastatic niche, exosomes and cGAS-STING, are reviewed.

Keywords: Exosomes; Head and neck; Hypoxia; Immune cells; Immune microenvironment; Immunotherapy; Inflammation; Lymphocytic response; Metabolism; STING; Stroma

References

  1. Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA Cancer J Clin 66:7–30 - PubMed
  2. Leemans CR, Braakhuis BJM, Brakenhoff RH (2011) The molecular biology of head and neck cancer. Nat Rev Cancer 11:9–22 - PubMed
  3. Gregoire V, Lefebvre J-L, Licitra L, Felip E (2010) Squamous cell carcinoma of the head and neck: EHNS-ESMO-ESTRO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 21:v184–v186 - PubMed
  4. Cancer IN du. Les cancers en France (2017) https://www.e-cancer.fr/Expertises-et-publications/Catalogue-des-publications/Les-cancers-en-France-Edition-2017 - PubMed
  5. Alsahafi E, Begg K, Amelio I, Raulf N, Lucarelli P, Sauter T et al (2019) Clinical update on head and neck cancer: molecular biology and ongoing challenges. Cell Death Dis 10:540 - PubMed
  6. Leemans CR, Snijders PJF, Brakenhoff RH (2018) The molecular landscape of head and neck cancer. Nat Rev Cancer 18:269–282 - PubMed
  7. Maxwell JH, Grandis JR, Ferris RL (2016) HPV-associated head and neck cancer: unique features of epidemiology and clinical management. Annu Rev Med 67:91–101 - PubMed
  8. Karpathiou G, Peoc’h M (2018) Immunohistochemical detection of p16 in clinical samples. Methods Mol Biol 1726:123–142 - PubMed
  9. Karpathiou G, Monaya A, Forest F, Froudarakis M, Casteillo F, Marc Dumollard J et al (2016) p16 and p53 expression status in head and neck squamous cell carcinoma: a correlation with histological, histoprognostic and clinical parameters. Pathology 48:341–348 - PubMed
  10. Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF et al (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363:24–35 - PubMed
  11. Weinberger PM, Yu Z, Haffty BG, Kowalski D, Harigopal M, Brandsma J et al (2006) Molecular classification identifies a subset of human papillomavirus–associated oropharyngeal cancers with favorable prognosis. J Clin Oncol 24:736–747 - PubMed
  12. Jou A, Hess J (2017) Epidemiology and molecular biology of head and neck Cancer. Oncol Res Treat 40:328–332 - PubMed
  13. Mukdad L, Heineman TE, Alonso J, Badran KW, Kuan EC, St John MA (2019) Oral tongue squamous cell carcinoma survival as stratified by age and sex: a surveillance, epidemiology, and end results analysis. Laryngoscope 129:2076–2081 - PubMed
  14. Sim F, Leidner R, Bell RB (2019) Immunotherapy for head and neck Cancer. Hematol Oncol Clin North Am 33:301–321 - PubMed
  15. Karpathiou G, Batistatou A, Forest F, Clemenson A, Peoc’h M (2016) Basic molecular pathology and cytogenetics for practicing pathologists: correlation with morphology and with a focus on aspects of diagnostic or therapeutic utility. Adv Anat Pathol 23:368–380 - PubMed
  16. Seiwert TY, Burtness B, Mehra R, Weiss J, Berger R, Eder JP et al (2016) 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 17:956–965 - PubMed
  17. Ferris RL, Blumenschein G, Fayette J, Guigay J, Colevas AD, Licitra L et al (2016) Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 375:1856–1867 - PubMed
  18. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674 - PubMed
  19. Mittal D, Gubin MM, Schreiber RD, Smyth MJ (2014) New insights into cancer immunoediting and its three component phases—elimination, equilibrium and escape. Curr Opin Immunol 27:16–25 - PubMed
  20. Tangye SG, Brink R (2012) A helping hand from neutrophils in T cell–independent antibody responses? Nat Immunol 13:111–113 - PubMed
  21. Fridlender ZG, Sun J, Kim S, Kapoor V, Cheng G, Ling L et al (2009) Polarization of tumor-associated neutrophil phenotype by TGF-β: “N1” versus “N2” TAN. Cancer Cell 16:183–194 - PubMed
  22. Peltanova B, Raudenska M, Masarik M (2019) Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review. Mol Cancer 18:63 - PubMed
  23. Gentles AJ, Newman AM, Liu CL, Bratman SV, Feng W, Kim D et al (2015) The prognostic landscape of genes and infiltrating immune cells across human cancers. Nat Med 21:938–945 - PubMed
  24. Anevlavis S, Kouliatsis G, Sotiriou I, Koukourakis MI, Archontogeorgis K, Karpathiou G et al (2014) Prognostic factors in patients presenting with pleural effusion revealing malignancy. Respiration 87:311–316 - PubMed
  25. Wisdom AJ, Hong CS, Lin AJ, Xiang Y, Cooper DE, Zhang J et al (2019) Neutrophils promote tumor resistance to radiation therapy. Proc Natl Acad Sci 116:18584–18589 - PubMed
  26. Zhang D, Zhou J, Tang D, Zhou L, Chou L, Chou K et al (2017) Neutrophil infiltration mediated by CXCL5 accumulation in the laryngeal squamous cell carcinoma microenvironment: a mechanism by which tumour cells escape immune surveillance. Clin Immunol 175:34–40 - PubMed
  27. Chen L, Zeng H, Yang J, Lu Y, Zhang D, Wang J et al (2018) Survival and prognostic analysis of preoperative inflammatory markers in patients undergoing surgical resection for laryngeal squamous cell carcinoma. BMC Cancer 18:816 - PubMed
  28. Du J, Liu J, Zhang X, Chen X, Yu R, Gu D (2017) et al, Pre-treatment neutrophil-to-lymphocyte ratio predicts survival in patients with laryngeal cancer. Oncol Lett 15: 1664-1672 - PubMed
  29. Wong BYW, Stafford ND, Green VL, Greenman J (2016) Prognostic value of the neutrophil-to-lymphocyte ratio in patients with laryngeal squamous cell carcinoma. Head Neck 38:E1903–E1908 - PubMed
  30. Tu X-P, Qiu Q-H, Chen L-S, Luo X-N, Lu Z-M, Zhang S-Y et al (2015) Preoperative neutrophil-to-lymphocyte ratio is an independent prognostic marker in patients with laryngeal squamous cell carcinoma. BMC Cancer 15:743 - PubMed
  31. Karpathiou G, Giroult J-B, Forest F, Fournel P, Monaya A, Froudarakis M et al (2016) Clinical and histologic predictive factors of response to induction chemotherapy in head and neck squamous cell carcinoma. Am J Clin Pathol 146:546–553 - PubMed
  32. Glogauer JE, Sun CX, Bradley G, Magalhaes MAO (2015) Neutrophils increase Oral squamous cell carcinoma invasion through an Invadopodia-dependent pathway. Cancer Immunol Res 3:1218–1226 - PubMed
  33. Decker P, Brenzel S, Droege H et al (2019) Prognostic role of blood NETosis in the progression of head and neck cancer. Cells 8:946 - PubMed
  34. Li B, Liu Y, Hu T, Zhang Y, Zhang C, Li T et al (2019) Neutrophil extracellular traps enhance procoagulant activity in patients with oral squamous cell carcinoma. J Cancer Res Clin Oncol 145:1695–1707 - PubMed
  35. Hinshaw DC, Shevde LA (2019) The tumor microenvironment innately modulates cancer progression. Cancer Res 79:4557–4566 - PubMed
  36. Seminerio I, Kindt N, Descamps G, Bellier J, Lechien JR, Mat Q et al (2018) High infiltration of CD68+ macrophages is associated with poor prognoses of head and neck squamous cell carcinoma patients and is influenced by human papillomavirus. Oncotarget 9: 11046–11059 - PubMed
  37. Karpathiou G, Casteillo F, Giroult J-B, Forest F, Fournel P, Monaya A et al (2017) Prognostic impact of immune microenvironment in laryngeal and pharyngeal squamous cell carcinoma: immune cell subtypes, immuno-suppressive pathways and clinicopathologic characteristics. Oncotarget 8:19310–19322 - PubMed
  38. Su C, Jia S, Liu H (2018) Immunolocalization of CD163+ tumor-associated macrophages and symmetric proliferation of Ki-67 as biomarkers to differentiate new different grades of laryngeal dysplasia. Am J Clin Pathol 149:8–16 - PubMed
  39. Sun W, Wei F-Q, Li W-J, Wei J-W, Zhong H, Wen Y-H et al (2017) A positive-feedback loop between tumour infiltrating activated Treg cells and type 2-skewed macrophages is essential for progression of laryngeal squamous cell carcinoma. Br J Cancer 117:1631–1643 - PubMed
  40. Yu D, Cheng J, Xue K, Zhao X, Wen L, Xu C (2018) Expression of programmed death-ligand 1 in laryngeal carcinoma and its effects on immune cell subgroup infiltration. Pathol Oncol Res 25: 1437–j91443 - PubMed
  41. Ai L, Mu S, Wang Y, Wang H, Cai L, Li W et al (2018) Prognostic role of myeloid-derived suppressor cells in cancers: a systematic review and meta-analysis. BMC Cancer 18:1220 - PubMed
  42. Wang Y, Ding Y, Guo N, Wang S (2019) MDSCs: key criminals of tumor pre-metastatic niche formation. Front Immunol 10: 172 - PubMed
  43. Ostrand-Rosenberg S, Beury DW, Parker KH, Horn LA (2019) Survival of the fittest: how myeloid-derived suppressor cells survive in the inhospitable tumor microenvironment. Cancer Immunol Immunother 69: 215–221 - PubMed
  44. Karpathiou G, Sivridis E, Koukourakis MI, Mikroulis D, Bouros D, Froudarakis ME et al (2011) Light-chain 3A autophagic activity and prognostic significance in non-small cell lung carcinomas. Chest 140:127–134 - PubMed
  45. Karpathiou G, Sivridis E, Koukourakis M, Mikroulis D, Bouros D, Froudarakis M et al (2013) Autophagy and Bcl-2/BNIP3 death regulatory pathway in non-small cell lung carcinomas. APMIS 121:592–604 - PubMed
  46. Chen W-C, Lai C-H, Chuang H-C, Lin P-Y, Chen M-F (2017) Inflammation-induced myeloid-derived suppressor cells associated with squamous cell carcinoma of the head and neck. Head Neck 39:347–355 - PubMed
  47. Mao L, Zhao Z, Yu G, Wu L, Deng W, Li Y et al (2018) γ-Secretase inhibitor reduces immunosuppressive cells and enhances tumour immunity in head and neck squamous cell carcinoma. Int J Cancer 142:999–1009 - PubMed
  48. Liu J-F, Deng W-W, Chen L, Li Y-C, Wu L, Ma S-R et al (2018) Inhibition of JAK2/STAT3 reduces tumor-induced angiogenesis and myeloid-derived suppressor cells in head and neck cancer. Mol Carcinog 57:429–439 - PubMed
  49. Zhang H, Liu L, Fu S, Liu Y-S, Wang C, Liu T et al (2017) Higher platelet distribution width predicts poor prognosis in laryngeal cancer. Oncotarget 8: 48138–48144 - PubMed
  50. Hsueh C, Tao L, Zhang M, Cao W, Gong H, Zhou J et al (2017) The prognostic value of preoperative neutrophils, platelets, lymphocytes, monocytes and calculated ratios in patients with laryngeal squamous cell cancer. Oncotarget 8: 60514–60527 - PubMed
  51. Stangl S, Tontcheva N, Sievert W, Shevtsov M, Niu M, Schmid TE et al (2018) Heat shock protein 70 and tumor-infiltrating NK cells as prognostic indicators for patients with squamous cell carcinoma of the head and neck after radiochemotherapy: a multicentre retrospective study of the German cancer consortium radiation oncology Gro. Int J Cancer 142:1911–1925 - PubMed
  52. Takami M, Ihara F, Motohashi S (2018) Clinical application of iNKT cell-mediated anti-tumor activity against lung cancer and head and neck cancer. Front Immunol 9: 2021 - PubMed
  53. Ogino T, Shigyo H, Ishii H, Katayama A, Miyokawa N, Harabuchi Y et al (2006) HLA class I antigen Down-regulation in primary laryngeal squamous cell carcinoma lesions as a poor prognostic marker. Cancer Res 66:9281–9289 - PubMed
  54. Guo Y, Liu J, Xu Z, Sun K, Fu W (2008) HLA-B gene participates in the NF-kappaB signal pathway partly by regulating S100A8 in the laryngeal carcinoma cell line Hep2. Oncol Rep 19:1453–1459 - PubMed
  55. Ma XJ, Pan XL, Lv ZH, Xu FL, Liu DY, Lei DP et al (2009) Therapeutic influence on circulating and monocyte-derived dendritic cells in laryngeal squamous cell carcinoma patients. Acta Otolaryngol 129:84–91 - PubMed
  56. Silva TG, Crispim JCO, Miranda FA, Hassumi MK, de Mello JMY, Simões RT et al (2011) Expression of the nonclassical HLA-G and HLA-E molecules in laryngeal lesions as biomarkers of tumor invasiveness. Histol Histopathol 26:1487–1497 - PubMed
  57. Klatka J, Grywalska E, Klatka M, Wasiak M, Andrzejczak A, Rolinski J (2013) Expression of selected regulatory molecules on the CD83+ monocyte-derived dendritic cells generated from patients with laryngeal cancer and their clinical significance. Eur Arch Oto-Rhino-Laryngol 270:2683–2693 - PubMed
  58. Chen L, Jin M, Li C, Shang Y, Zhang Q (2017) The tissue distribution and significance of B7-H4 in laryngeal carcinoma. Oncotarget 88: 92227–92239 - PubMed
  59. Yum S, Li M, Frankel AE, Chen ZJ (2019) Roles of the cGAS-STING pathway in cancer immunosurveillance and immunotherapy. Annu Rev Cancer Biol 3:323–344 - PubMed
  60. Bakhoum SF, Ngo B, Laughney AM, Cavallo J-A, Murphy CJ, Ly P et al (2018) Chromosomal instability drives metastasis through a cytosolic DNA response. Nature 553:467–472 - PubMed
  61. Lu S, Concha-Benavente F, Shayan G, Srivastava RM, Gibson SP, Wang L et al (2018) STING activation enhances cetuximab-mediated NK cell activation and DC maturation and correlates with HPV + status in head and neck cancer. Oral Oncol 78:186–193 - PubMed
  62. Shaikh MH, Bortnik V, McMillan NA, Idris A (2019) cGAS-STING responses are dampened in high-risk HPV type 16 positive head and neck squamous cell carcinoma cells. Microb Pathog 132:162–165 - PubMed
  63. Plzák J, Bouček J, Bandúrová V, Kolář M, Hradilová M, Szabo P et al (2019) The head and neck squamous cell carcinoma microenvironment as a potential target for cancer therapy. Cancers (Basel) 11:440 - PubMed
  64. da Silva JM, Soave DF (2016) Moreira dos Santos TP, Batista AC, Russo RC, Teixeira MM, et al. significance of chemokine and chemokine receptors in head and neck squamous cell carcinoma: a critical review. Oral Oncol 56:8–16 - PubMed
  65. Albert S, Riveiro ME, Halimi C, Hourseau M, Couvelard A, Serova M et al (2013) Focus on the role of the CXCL12/CXCR4 chemokine axis in head and neck squamous cell carcinoma. Myers JN, editor. Head Neck 35:1819–1828 - PubMed
  66. Wortzel I, Dror S, Kenific CM, Lyden D (2019) Exosome-mediated metastasis: communication from a distance. Dev Cell 49:347–360 - PubMed
  67. Guo Y, Ji X, Liu J, Fan D, Zhou Q, Chen C et al (2019) Effects of exosomes on pre-metastatic niche formation in tumors. Mol Cancer 18:39 - PubMed
  68. Ludwig S, Marczak L, Sharma P, Abramowicz A, Gawin M, Widlak P et al (2019) Proteomes of exosomes from HPV(+) or HPV(−) head and neck cancer cells: differential enrichment in immunoregulatory proteins. Onco Targets Ther 8:1593808 - PubMed
  69. Ludwig S, Sharma P, Theodoraki M-N, Pietrowska M, Yerneni SS, Lang S et al (2018) Molecular and functional profiles of Exosomes from HPV(+) and HPV(−) head and neck Cancer cell lines. Front Oncol 8: 445 - PubMed
  70. Theodoraki M-N, Yerneni SS, Hoffmann TK, Gooding WE, Whiteside TL (2018) Clinical significance of PD-L1 + exosomes in plasma of head and neck Cancer patients. Clin Cancer Res 24:896–905 - PubMed
  71. Zhang G, Fan E, Zhong Q, Feng G, Shuai Y, Wu M et al (2019) Identification and potential mechanisms of a 4-lncRNA signature that predicts prognosis in patients with laryngeal cancer. Hum Genomics 13:36 - PubMed
  72. Gong H-L, Shi Y, Zhou L, Wu C-P, Cao P-Y, Tao L et al (2013) The composition of microbiome in larynx and the throat biodiversity between laryngeal squamous cell carcinoma patients and control population. Emmert-Buck MR, editor. PLoS One 8:e66476 - PubMed
  73. Gong H, Shi Y, Xiao X, Cao P, Wu C, Tao L et al (2017) Alterations of microbiota structure in the larynx relevant to laryngeal carcinoma. Sci Rep 7:5507 - PubMed
  74. Forster MD, Devlin M-J (2018) Immune checkpoint inhibition in head and neck cancer. Front Oncol 8: 310 - PubMed
  75. Blank CU, Haanen JB, Ribas A, Schumacher TN (2016) The “cancer immunogram”. Science (80) 352:658–660 - PubMed
  76. Jia Y-Q, Yang B, Wen L-L, Mu W-X, Wang Z, Cheng B (2019) Prognostic value of immune checkpoint molecules in head and neck cancer: a meta-analysis. Aging (Albany NY) 11:501–522 - PubMed
  77. Birtalan E, Danos K, Gurbi B, Brauswetter D, Halasz J, Kalocsane Piurko V et al (2018) Expression of PD-L1 on immune cells shows better prognosis in laryngeal, Oropharygeal, and Hypopharyngeal Cancer. Appl Immunohistochem Mol Morphol 26:e79–e85 - PubMed
  78. Malm I-J, Rooper LM, Bishop JA, Ozgursoy SK, Hillel AT, Akst LM et al (2019) Molecular and immunologic analysis of laryngeal squamous cell carcinoma in smokers and non-smokers. Am J Otolaryngol 40:213–217 - PubMed
  79. Rasmussen JH, Lelkaitis G, Håkansson K, Vogelius IR, Johannesen HH, Fischer BM et al (2019) Intratumor heterogeneity of PD-L1 expression in head and neck squamous cell carcinoma. Br J Cancer 120:1003–1006 - PubMed
  80. Cohen EEW, Bell RB, Bifulco CB, Burtness B, Gillison ML, Harrington KJ et al (2019) The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC). J Immunother Cancer 7:184 - PubMed
  81. Allen CT, Lee S, Norberg SM, Kovalovsky D, Ye H, Clavijo PE et al (2019) Safety and clinical activity of PD-L1 blockade in patients with aggressive recurrent respiratory papillomatosis. J Immunother Cancer 7:119 - PubMed
  82. Ahn J, Bishop JA, Roden RBS, Allen CT, Best SRA (2018) The PD-1 and PD-L1 pathway in recurrent respiratory papillomatosis. Laryngoscope 128:E27–E32 - PubMed
  83. Schumacher TN, Scheper W, Kvistborg P (2019) Cancer Neoantigens. Annu Rev Immunol 37:173–200 - PubMed
  84. Eder T, Hess AK, Konschak R, Stromberger C, Jöhrens K, Fleischer V et al (2019) Interference of tumour mutational burden with outcome of patients with head and neck cancer treated with definitive chemoradiation: a multicentre retrospective study of the German Cancer consortium radiation oncology group. Eur J Cancer 116:67–76 - PubMed
  85. Faden DL, Ding F, Lin Y, Zhai S, Kuo F, Chan TA et al (2019) APOBEC mutagenesis is tightly linked to the immune landscape and immunotherapy biomarkers in head and neck squamous cell carcinoma. Oral Oncol 96:140–147 - PubMed
  86. FDA. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm560167.htm - PubMed
  87. Koy S, Plaschke J, Luksch H, Friedrich K, Kuhlisch E, Eckelt U et al (2008) Microsatellite instability and loss of heterozygosity in squamous cell carcinoma of the head and neck. Head Neck 30:1105–1113 - PubMed
  88. Demokan S, Suoglu Y, Demir D, Gozeler M, Dalay N (2006) Microsatellite instability and methylation of the DNA mismatch repair genes in head and neck cancer. Ann Oncol 17:995–999 - PubMed
  89. De Schutter H, Spaepen M, Van Opstal S, Vander Poorten V, Verbeken E, Nuyts S (2009) The prevalence of microsatellite instability in head and neck squamous cell carcinoma. J Cancer Res Clin Oncol 135:485–490 - PubMed
  90. Lin J-C, Wang C-C, Jiang R-S, Wang W-Y, Liu S-A (2016) Microsatellite alteration in head and neck squamous cell carcinoma patients from a betel quid-prevalent region. Sci Rep 6:22614 - PubMed
  91. Colevas AD, Bahleda R, Braiteh F, Balmanoukian A, Brana I, Chau NG et al (2018) Safety and clinical activity of atezolizumab in head and neck cancer: results from a phase I trial. Ann Oncol 29:2247–2253 - PubMed
  92. Li L, Cao B, Liang X, Lu S, Luo H, Wang Z et al (2019) Microenvironmental oxygen pressure orchestrates an anti- and pro-tumoral γδ T cell equilibrium via tumor-derived exosomes. Oncogene 38:2830–2843 - PubMed
  93. Zou W, Shah YM (2019) A PHD in immunosuppression: oxygen-sensing pathways regulate immunosuppressive Tregs. J Clin Invest 129:3524–3526 - PubMed
  94. Hatam LJ, DeVoti JA, Rosenthal DW, Lam F, Abramson AL, Steinberg BM et al (2012) Immune suppression in premalignant respiratory Papillomas: enriched functional CD4+Foxp3+ regulatory T cells and PD-1/PD-L1/L2 expression. Clin Cancer Res 18:1925–1935 - PubMed
  95. Zappasodi R, Sirard C, Li Y, Budhu S, Abu-Akeel M, Liu C et al (2019) Rational design of anti-GITR-based combination immunotherapy. Nat Med 25:759–766 - PubMed
  96. McLane LM, Abdel-Hakeem MS, Wherry EJ (2019) CD8 T cell exhaustion during chronic viral infection and Cancer. Annu Rev Immunol 37:457–495 - PubMed
  97. Outh-Gauer S, Morini A, Tartour E, Lépine C, Jung AC, Badoual C (2020) The microenvironment of head and neck cancers: papillomavirus involvement and potential impact of immunomodulatory treatments. Head Neck Pathol 14: 330–340 - PubMed
  98. Chen L, Yang Q-C, Li Y-C, Yang L-L, Liu J-F, Li H et al (2020) Targeting CMTM6 suppresses stem cell–like properties and enhances antitumor immunity in head and neck squamous cell carcinoma. Cancer Immunol Res 8:179–191 - PubMed
  99. Karpathiou G, Vieville M, Gavid M, Camy F, Dumollard JM, Magné N et al (2019) Prognostic significance of tumor budding, tumor-stroma ratio, cell nests size, and stroma type in laryngeal and pharyngeal squamous cell carcinomas. Head Neck 41:1918–1927 - PubMed
  100. Karpathiou G, Gavid M, Prevot-Bitot N, Dhomps A, Dumollard JM, Vieville M et al (2019) Correlation between semiquantitative metabolic parameters after PET/CT and histologic prognostic factors in laryngeal and pharyngeal carcinoma. Head Neck Pathol 14: 724–732 - PubMed
  101. Takahashi H, Sakakura K, Kawabata-Iwakawa R, Rokudai S, Toyoda M, Nishiyama M et al (2015) Immunosuppressive activity of cancer-associated fibroblasts in head and neck squamous cell carcinoma. Cancer Immunol Immunother 64:1407–1417 - PubMed
  102. Hui L, Zhang J, Ding X, Guo X, Jiang X (2017) Matrix stiffness regulates the proliferation, stemness and chemoresistance of laryngeal squamous cancer cells. Int J Oncol 50:1439–1447 - PubMed
  103. Cappellesso R, Marioni G, Crescenzi M, Giacomelli L, Guzzardo V, Mussato A et al (2015) The prognostic role of the epithelial-mesenchymal transition markers E-cadherin and slug in laryngeal squamous cell carcinoma. Histopathology 67:491–500 - PubMed
  104. Zhu G, Song P, Zhou H, Shen X, Wang J, Ma X et al (2018) Role of epithelial-mesenchymal transition markers E-cadherin, N-cadherin, β-catenin and ZEB2 in laryngeal squamous cell carcinoma. Oncol Lett 15:3472–3481 - PubMed
  105. Schlüter A, Weller P, Kanaan O, Nel I, Heusgen L, Höing B et al (2018) CD31 and VEGF are prognostic biomarkers in early-stage, but not in late-stage, laryngeal squamous cell carcinoma. BMC Cancer 18:272 - PubMed
  106. Bolzoni Villaret A, Barbieri D, Peretti G, Schreiber A, Fisogni S, Lonardi S et al (2013) Angiogenesis and lymphangiogenesis in early-stage laryngeal carcinoma: prognostic implications. Head Neck 35:1132–1137 - PubMed
  107. Amit M, Na’ara S, Gil Z (2016) Mechanisms of cancer dissemination along nerves. Nat Rev Cancer 16:399–408 - PubMed
  108. Roh J, Muelleman T, Tawfik O, Thomas SM (2015) Perineural growth in head and neck squamous cell carcinoma: a review. Oral Oncol 51:16–23 - PubMed
  109. Amit M, Eran A, Billan S, Fridman E, Na’ara S, Charas T et al (2016) Perineural spread in noncutaneous head and neck Cancer: new insights into an old problem. J Neurol Surg Part B Skull Base 77:086–095 - PubMed
  110. Scanlon CS, Banerjee R, Inglehart RC, Liu M, Russo N, Hariharan A et al (2015) Galanin modulates the neural niche to favour perineural invasion in head and neck cancer. Nat Commun 6:6885 - PubMed
  111. Misawa K, Mima M, Imai A, Mochizuki D, Misawa Y, Endo S et al (2018) The neuropeptide genes SST, TAC1, HCRT, NPY, and GAL are powerful epigenetic biomarkers in head and neck cancer: a site-specific analysis. Clin Epigenetics 10:52 - PubMed
  112. Madeo M, Colbert PL, Vermeer DW, Lucido CT, Cain JT, Vichaya EG et al (2018) Cancer exosomes induce tumor innervation. Nat Commun 9:4284 - PubMed
  113. Prazeres P, Leonel C, Silva W, Rocha B, Santos G, Costa A et al (2020) Ablation of sensory nerves favours melanoma progression. J Cell Mol Med:1–13 - PubMed
  114. Gong L, Zhang W, Zhou J, Lu J, Xiong H, Shi X et al (2013) Prognostic Value of HIFs Expression in Head and Neck Cancer: A Systematic Review. Tu Y-K, editor. PLoS One 8:e75094 - PubMed
  115. Curry JM, Tuluc M, Whitaker-Menezes D, Ames JA, Anantharaman A, Butera A et al (2013) Cancer metabolism, stemness and tumor recurrence. Cell Cycle 12:1371–1384 - PubMed
  116. Karpathiou G, Stachowitz M-L, Dumollard JM, Gavid M, Froudarakis M, Prades JM et al (2019) Gene expression comparison between the primary tumor and its lymph node metastasis in head and neck squamous cell carcinoma: a pilot study. Cancer Genomics Proteomics 16:155–161 - PubMed
  117. Jing B, Wang T, Sun B, Xu J, Xu D, Liao Y et al (2020) IL6/STAT3 signaling orchestrates Premetastatic niche formation and immunosuppressive traits in lung. Cancer Res 80:784–797 - PubMed
  118. Ghouse SM, Vadrevu SK, Manne S, Reese B, Patel J, Patel B et al (2020) Therapeutic targeting of vasculature in the Premetastatic and metastatic niches reduces lung metastasis. J Immunol 204:990–1000 - PubMed
  119. Mabuchi S, Komura N, Sasano T, Shimura K, Yokoi E, Kozasa K et al (2020) Pretreatment tumor-related leukocytosis misleads positron emission tomography-computed tomography during lymph node staging in gynecological malignancies. Nat Commun 11:1364 - PubMed
  120. Lu Z, Zou J, Li S, Topper MJ, Tao Y, Zhang H et al (2020) Epigenetic therapy inhibits metastases by disrupting premetastatic niches. Nature 579:284–290 - PubMed
  121. Cheng R, Billet S, Liu C, Haldar S, Choudhury D, Tripathi M et al (2020) Periodontal inflammation recruits distant metastatic breast cancer cells by increasing myeloid-derived suppressor cells. Oncogene 39:1543–1556 - PubMed
  122. Chang M-C, Chan C-P, Ho Y-S, Lee J-J, Lin P-S, Lin B-R et al (2008) Signaling pathways for induction of platelet aggregation by SAS tongue cancer cells - a mechanism of hematogenous metastasis. J Oral Pathol Med 38:434–440 - PubMed
  123. Ye J, Liu H, Hu Y, Li P, Zhang G, Li Y (2013) Tumoral indoleamine 2,3-dioxygenase expression predicts poor outcome in laryngeal squamous cell carcinoma. Virchows Arch 462:73–81 - PubMed

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