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Recent Advances in Head and Neck Tumor Microenvironment–Based Therapy

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Tumor Microenvironments in Organs

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1296))

Abstract

Head and neck squamous cell carcinomas (HNSCCs) are a group of heterogeneous aggressive tumors affecting more than half a million patients worldwide annually. While the tobacco- and alcohol-associated HNSCC tumors are declining, human papillomavirus (HPV)-induced tumors are on rise. Despite recent advances in multimodality therapeutic interventions including surgery in combination with chemoradiation therapy (CRT), the overall 5-year survival has not improved more than 50%. The underlying reasons for this dismal prognosis is the intrinsic or acquired resistance to CRT. While previous studies were focused to target tumor cells, recent findings have implicated the involvement of tumor microenvironment (TME) on tumor progression and response to therapy. HNSCC TME includes cancer-associated fibroblasts (CAFs), endothelial cells, immune cells, endocrine cells, and the extracellular matrix (ECM) proteins including collagen and fibronectin. Understanding the crosstalk between TME and cancer cells is important to formulate more effective novel therapies and to overcome resistance mechanisms. Here, we summarized the current literature on recent advances on HNSCC TME with special emphasis on novel cell–cell interactions and therapies currently under development.

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Abbreviations

CAF :

Cancer-associated fibroblasts

CSF-1 :

Colony-stimulating factor-1

DC :

Dendritic cell

ECM :

Extracellular matrix

EGF :

Epidermal growth factor

Fas-L :

Fas ligand

FGF :

Fibroblast growth factor

FoxP3 :

Forked/winghead transcription factor

G-CSF :

Granulocyte colony-stimulating factor

GM-CSF :

Granulocyte-macrophage colony-stimulating factor

HGF :

Hepatocyte growth factor

HNSCC :

Head and neck squamous cell carcinoma

IL :

Interleukin

MDSC :

Myeloid-derived suppressor cell

MMP :

Matrix metallo protein

NK :

Natural killer cell

ORR :

Overall response rate

OS :

Overall survival

PD-1 :

Programmed death-1

PDGF :

Platelet-derived growth factor

PD-L1 :

Programmed death ligand-1

PFS :

Progression free survival

PGE :

Prostaglandin

RNS :

Reactive nitrogen species

ROS :

Reactive oxygen species

TAM :

Tumor-associated macrophage

TCR :

T cell receptor

TGF :

Transforming growth factor

TME :

Tumor microenvironment

TNF-α :

Tumor necrosis factor-α

VEGF :

Vascular endothelial growth factor

References

  1. Fitzmaurice C, Allen C, Barber RM, Barregard L, Bhutta ZA, Brenner H, Dicker DJ, Chimed-Orchir O, Dandona R, Dandona L et al (2017) Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study. JAMA Oncol 3(4):524–548

    Article  PubMed  Google Scholar 

  2. Ghantous Y, Abu Elnaaj I (2017) Global incidence and risk factors of oral cancer. Harefuah 156(10):645–649

    PubMed  Google Scholar 

  3. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424

    Article  PubMed  Google Scholar 

  4. Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68(1):7–30

    Article  PubMed  Google Scholar 

  5. Leemans CR, Snijders PJF, Brakenhoff RH (2018) The molecular landscape of head and neck cancer. Nat Rev Cancer 18(5):269–282

    Article  CAS  PubMed  Google Scholar 

  6. Fakhry C, Gillison ML (2006) Clinical implications of human papillomavirus in head and neck cancers. J Clin Oncol Off J Am Soc Clin Oncol 24(17):2606–2611

    Article  Google Scholar 

  7. Hashibe M, Brennan P, Chuang SC, Boccia S, Castellsague X, Chen C, Curado MP, Dal Maso L, Daudt AW, Fabianova E et al (2009) Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Cancer Epidemiol Biomarkers Prev 18(2):541–550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Maier H, Dietz A, Gewelke U, Heller WD, Weidauer H (1992) Tobacco and alcohol and the risk of head and neck cancer. Clin Investig 70(3–4):320–327

    CAS  PubMed  Google Scholar 

  9. Sturgis EM, Wei Q (2002) Genetic susceptibility--molecular epidemiology of head and neck cancer. Curr Opin Oncol 14(3):310–317

    Article  PubMed  Google Scholar 

  10. Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, Jiang B, Goodman MT, Sibug-Saber M, Cozen W et al (2011) Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol Off J Am Soc Clin Oncol 29(32):4294–4301

    Article  Google Scholar 

  11. Martin L, Zoubir M, Le Tourneau C (2014) Recurrence of upper aerodigestive tract tumors. Bull Cancer 101(5):511–520

    Article  PubMed  Google Scholar 

  12. Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C et al (2016) Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 375(19):1856–1867

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. da Silva IP, Gallois A, Jimenez-Baranda S, Khan S, Anderson AC, Kuchroo VK, Osman I, Bhardwaj N (2014) Reversal of NK-cell exhaustion in advanced melanoma by Tim-3 blockade. Cancer Immunol Res 2(5):410–422

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Whiteside TL (2005) Immunobiology of head and neck cancer. Cancer Metastasis Rev 24(1):95–105

    Article  CAS  PubMed  Google Scholar 

  15. Chikamatsu K, Sakakura K, Toyoda M, Takahashi K, Yamamoto T, Masuyama K (2012) Immunosuppressive activity of CD14+ HLA-DR- cells in squamous cell carcinoma of the head and neck. Cancer Sci 103(6):976–983

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Marcus B, Arenberg D, Lee J, Kleer C, Chepeha DB, Schmalbach CE, Islam M, Paul S, Pan Q, Hanash S et al (2004) Prognostic factors in oral cavity and oropharyngeal squamous cell carcinoma. Cancer 101(12):2779–2787

    Article  PubMed  Google Scholar 

  17. Wolf GT, Chepeha DB, Bellile E, Nguyen A, Thomas D, McHugh J (2015) Tumor infiltrating lymphocytes (TIL) and prognosis in oral cavity squamous carcinoma: a preliminary study. Oral Oncol 51(1):90–95

    Article  CAS  PubMed  Google Scholar 

  18. Tsukishiro T, Donnenberg AD, Whiteside TL (2003) Rapid turnover of the CD8(+)CD28(−) T-cell subset of effector cells in the circulation of patients with head and neck cancer. Cancer Immunol Immunother: CII 52(10):599–607

    Article  PubMed  Google Scholar 

  19. Varilla V, Atienza J, Dasanu CA (2013) Immune alterations and immunotherapy prospects in head and neck cancer. Expert Opin Biol Ther 13(9):1241–1256

    Article  CAS  PubMed  Google Scholar 

  20. Erez N, Truitt M, Olson P, Arron ST, Hanahan D (2010) Cancer-associated fibroblasts are activated in incipient neoplasia to orchestrate tumor-promoting inflammation in an NF-kappaB-dependent manner. Cancer Cell 17(2):135–147

    Article  CAS  PubMed  Google Scholar 

  21. Kalluri R (2016) The biology and function of fibroblasts in cancer. Nat Rev Cancer 16(9):582–598

    Article  CAS  PubMed  Google Scholar 

  22. Gascard P, Tlsty TD (2016) Carcinoma-associated fibroblasts: orchestrating the composition of malignancy. Genes Dev 30(9):1002–1019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Sugimoto H, Mundel TM, Kieran MW, Kalluri R (2006) Identification of fibroblast heterogeneity in the tumor microenvironment. Cancer Biol Ther 5(12):1640–1646

    Article  CAS  PubMed  Google Scholar 

  24. Marsh D, Suchak K, Moutasim KA, Vallath S, Hopper C, Jerjes W, Upile T, Kalavrezos N, Violette SM, Weinreb PH et al (2011) Stromal features are predictive of disease mortality in oral cancer patients. J Pathol 223(4):470–481

    Article  CAS  PubMed  Google Scholar 

  25. Wheeler SE, Shi H, Lin F, Dasari S, Bednash J, Thorne S, Watkins S, Joshi R, Thomas SM (2014) Enhancement of head and neck squamous cell carcinoma proliferation, invasion, and metastasis by tumor-associated fibroblasts in preclinical models. Head Neck 36(3):385–392

    Article  PubMed  Google Scholar 

  26. De Wever O, Nguyen QD, Van Hoorde L, Bracke M, Bruyneel E, Gespach C, Mareel M (2004) Tenascin-C and SF/HGF produced by myofibroblasts in vitro provide convergent pro-invasive signals to human colon cancer cells through RhoA and Rac. FASEB J 18(9):1016–1018

    Article  PubMed  CAS  Google Scholar 

  27. Orimo A, Weinberg RA (2007) Heterogeneity of stromal fibroblasts in tumors. Cancer Biol Ther 6(4):618–619

    Article  CAS  PubMed  Google Scholar 

  28. Kikuchi Y, Kashima TG, Nishiyama T, Shimazu K, Morishita Y, Shimazaki M, Kii I, Horie H, Nagai H, Kudo A et al (2008) Periostin is expressed in pericryptal fibroblasts and cancer-associated fibroblasts in the colon. J Histochem Cytochem 56(8):753–764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Pietras K, Sjoblom T, Rubin K, Heldin CH, Ostman A (2003) PDGF receptors as cancer drug targets. Cancer Cell 3(5):439–443

    Article  CAS  PubMed  Google Scholar 

  30. Li M, Li M, Yin T, Shi H, Wen Y, Zhang B, Chen M, Xu G, Ren K, Wei Y (2016) Targeting of cancerassociated fibroblasts enhances the efficacy of cancer chemotherapy by regulating the tumor microenvironment. Mol Med Rep 13(3):2476–2484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Oliveira-Neto HH, Silva ET, Leles CR, Mendonca EF, Alencar Rde C, Silva TA, Batista AC (2008) Involvement of CXCL12 and CXCR4 in lymph node metastases and development of oral squamous cell carcinomas. Tumour Biol 29(4):262–271

    Article  CAS  PubMed  Google Scholar 

  32. Schmitz S, Bindea G, Albu RI, Mlecnik B, Machiels JP (2015) Cetuximab promotes epithelial to mesenchymal transition and cancer associated fibroblasts in patients with head and neck cancer. Oncotarget 6(33):34288–34299

    Article  PubMed  PubMed Central  Google Scholar 

  33. Onoue T, Uchida D, Begum NM, Tomizuka Y, Yoshida H, Sato M (2006) Epithelial-mesenchymal transition induced by the stromal cell-derived factor-1/CXCR4 system in oral squamous cell carcinoma cells. Int J Oncol 29(5):1133–1138

    CAS  PubMed  Google Scholar 

  34. Yoon Y, Liang Z, Zhang X, Choe M, Zhu A, Cho HT, Shin DM, Goodman MM, Chen ZG, Shim H (2007) CXC chemokine receptor-4 antagonist blocks both growth of primary tumor and metastasis of head and neck cancer in xenograft mouse models. Cancer Res 67(15):7518–7524

    Article  CAS  PubMed  Google Scholar 

  35. Koontongkaew S, Amornphimoltham P, Monthanpisut P, Saensuk T, Leelakriangsak M (2012) Fibroblasts and extracellular matrix differently modulate MMP activation by primary and metastatic head and neck cancer cells. Med Oncol (Northwood, London, England) 29(2):690–703

    Article  CAS  Google Scholar 

  36. Liang Z, Brooks J, Willard M, Liang K, Yoon Y, Kang S, Shim H (2007) CXCR4/CXCL12 axis promotes VEGF-mediated tumor angiogenesis through Akt signaling pathway. Biochem Biophys Res Commun 359(3):716–722

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Yu T, Wu Y, Huang Y, Yan C, Liu Y, Wang Z, Wang X, Wen Y, Wang C, Li L (2012) RNAi targeting CXCR4 inhibits tumor growth through inducing cell cycle arrest and apoptosis. Mol Ther 20(2):398–407

    Article  CAS  PubMed  Google Scholar 

  38. Canning M, Guo G, Yu M, Myint C, Groves MW, Byrd JK, Cui Y (2019) Heterogeneity of the head and neck squamous cell carcinoma immune landscape and its impact on immunotherapy. Front Cell Dev Biol 7:52

    Article  PubMed  PubMed Central  Google Scholar 

  39. 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(1):63

    Article  PubMed  PubMed Central  Google Scholar 

  40. Galdiero MR, Garlanda C, Jaillon S, Marone G, Mantovani A (2013) Tumor associated macrophages and neutrophils in tumor progression. J Cell Physiol 228(7):1404–1412

    Article  CAS  PubMed  Google Scholar 

  41. Kikuchi K, Kusama K, Taguchi K, Ishikawa F, Okamoto M, Shimada J, Sakashita H, Yamamo Y (2002) Dendritic cells in human squamous cell carcinoma of the oral cavity. Anticancer Res 22(2a):545–557

    CAS  PubMed  Google Scholar 

  42. Curry JM, Sprandio J, Cognetti D, Luginbuhl A, Bar-ad V, Pribitkin E, Tuluc M (2014) Tumor microenvironment in head and neck squamous cell carcinoma. Semin Oncol 41(2):217–234

    Article  CAS  PubMed  Google Scholar 

  43. Hanna GJ, Liu H, Jones RE, Bacay AF, Lizotte PH, Ivanova EV, Bittinger MA, Cavanaugh ME, Rode AJ, Schoenfeld JD et al (2017) Defining an inflamed tumor immunophenotype in recurrent, metastatic squamous cell carcinoma of the head and neck. Oral Oncol 67:61–69

    Article  CAS  PubMed  Google Scholar 

  44. Badoual C, Hans S, Merillon N, Van Ryswick C, Ravel P, Benhamouda N, Levionnois E, Nizard M, Si-Mohamed A, Besnier N et al (2013) PD-1-expressing tumor-infiltrating T cells are a favorable prognostic biomarker in HPV-associated head and neck cancer. Cancer Res 73(1):128–138

    Article  CAS  PubMed  Google Scholar 

  45. Paneesha S, McManus A, Arya R, Scriven N, Farren T, Nokes T, Bacon S, Nieland A, Cooper D, Smith H et al (2010) Frequency, demographics and risk (according to tumour type or site) of cancer-associated thrombosis among patients seen at outpatient DVT clinics. Thromb Haemost 103(2):338–343

    Article  CAS  PubMed  Google Scholar 

  46. Molling JW, Langius JA, Langendijk JA, Leemans CR, Bontkes HJ, van der Vliet HJ, von Blomberg BM, Scheper RJ, van den Eertwegh AJ (2007) Low levels of circulating invariant natural killer T cells predict poor clinical outcome in patients with head and neck squamous cell carcinoma. J Clin Oncol 25(7):862–868

    Article  PubMed  Google Scholar 

  47. Schneiders FL, de Bruin RC, van den Eertwegh AJ, Scheper RJ, Leemans CR, Brakenhoff RH, Langendijk JA, Verheul HM, de Gruijl TD, Molling JW et al (2012) Circulating invariant natural killer T-cell numbers predict outcome in head and neck squamous cell carcinoma: updated analysis with 10-year follow-up. J Clin Oncol Off J Am Soc Clin Oncol 30(5):567–570

    Article  Google Scholar 

  48. Eilken HM, Dieguez-Hurtado R, Schmidt I, Nakayama M, Jeong HW, Arf H, Adams S, Ferrara N, Adams RH (2017) Pericytes regulate VEGF-induced endothelial sprouting through VEGFR1. Nat Commun 8(1):1574

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Huang H, Bhat A, Woodnutt G, Lappe R (2010) Targeting the ANGPT-TIE2 pathway in malignancy. Nat Rev Cancer 10(8):575–585

    Article  CAS  PubMed  Google Scholar 

  50. Birbrair A, Zhang T, Wang ZM, Messi ML, Olson JD, Mintz A, Delbono O (2014) Type-2 pericytes participate in normal and tumoral angiogenesis. Am J Physiol Cell Physiol 307(1):C25–C38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Pietras K, Ostman A (2010) Hallmarks of cancer: interactions with the tumor stroma. Exp Cell Res 316(8):1324–1331

    Article  CAS  PubMed  Google Scholar 

  52. Roma-Rodrigues C, Mendes R, Baptista PV, Fernandes AR (2019) Targeting tumor microenvironment for cancer therapy. Int J Mol Sci 20(4)

    Google Scholar 

  53. Zhang J, Liu J (2013) Tumor stroma as targets for cancer therapy. Pharmacol Ther 137(2):200–215

    Article  CAS  PubMed  Google Scholar 

  54. Ziober AF, Falls EM, Ziober BL (2006) The extracellular matrix in oral squamous cell carcinoma: friend or foe? Head Neck 28(8):740–749

    Article  PubMed  Google Scholar 

  55. Harada T, Shinohara M, Nakamura S, Oka M (1994) An immunohistochemical study of the extracellular matrix in oral squamous cell carcinoma and its association with invasive and metastatic potential. Virchows Archiv 424(3):257–266

    Article  CAS  PubMed  Google Scholar 

  56. Fabricius EM, Wildner GP, Kruse-Boitschenko U, Hoffmeister B, Goodman SL, Raguse JD (2011) Immunohistochemical analysis of integrins alphavbeta3, alphavbeta5 and alpha5beta1, and their ligands, fibrinogen, fibronectin, osteopontin and vitronectin, in frozen sections of human oral head and neck squamous cell carcinomas. Exp Ther Med 2(1):9–19

    Article  CAS  PubMed  Google Scholar 

  57. Prazeres P, Leonel C, Silva WN, Rocha BGS, Santos GSP, Costa AC, Picoli CC, Sena IFG, Gonçalves WA, Vieira MS et al (2020) Ablation of sensory nerves favours melanoma progression. J Cell Mol Med

    Google Scholar 

  58. Kaucká M, Adameyko I (2014) Non-canonical functions of the peripheral nerve. Exp Cell Res 321(1):17–24

    Article  PubMed  CAS  Google Scholar 

  59. Bapat AA, Hostetter G, Von Hoff DD, Han H (2011) Perineural invasion and associated pain in pancreatic cancer. Nat Rev Cancer 11(10):695–707

    Article  CAS  PubMed  Google Scholar 

  60. Roh J, Muelleman T, Tawfik O, Thomas SM (2015) Perineural growth in head and neck squamous cell carcinoma: a review. Oral Oncol 51(1):16–23

    Article  PubMed  Google Scholar 

  61. Zhao CM, Hayakawa Y, Kodama Y, Muthupalani S, Westphalen CB, Andersen GT, Flatberg A, Johannessen H, Friedman RA, Renz BW et al (2014) Denervation suppresses gastric tumorigenesis. Sci Transl Med 6(250):250ra115

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Schmitd LB, Scanlon CS, D'Silva NJ (2018) Perineural invasion in head and neck cancer. J Dent Res 97(7):742–750

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Tarsitano A, Tardio ML, Marchetti C (2015) Impact of perineural invasion as independent prognostic factor for local and regional failure in oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol 119(2):221–228

    Article  PubMed  Google Scholar 

  64. Teichgraber V, Monasterio C, Chaitanya K, Boger R, Gordon K, Dieterle T, Jager D, Bauer S (2015) Specific inhibition of fibroblast activation protein (FAP)-alpha prevents tumor progression in vitro. Adv Med Sci 60(2):264–272

    Article  PubMed  Google Scholar 

  65. Qin X, Yan M, Zhang J, Wang X, Shen Z, Lv Z, Li Z, Wei W, Chen W (2016) TGFbeta3-mediated induction of Periostin facilitates head and neck cancer growth and is associated with metastasis. Sci Rep 6:20587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Kyutoku M, Taniyama Y, Katsuragi N, Shimizu H, Kunugiza Y, Iekushi K, Koibuchi N, Sanada F, Oshita Y, Morishita R (2011) Role of periostin in cancer progression and metastasis: inhibition of breast cancer progression and metastasis by anti-periostin antibody in a murine model. Int J Mol Med 28(2):181–186

    CAS  PubMed  Google Scholar 

  67. Zhu M, Saxton RE, Ramos L, Chang DD, Karlan BY, Gasson JC, Slamon DJ (2011) Neutralizing monoclonal antibody to periostin inhibits ovarian tumor growth and metastasis. Mol Cancer Ther 10(8):1500–1508

    Article  CAS  PubMed  Google Scholar 

  68. Kumar D, Kandl C, Hamilton CD, Shnayder Y, Tsue TT, Kakarala K, Ledgerwood L, Sun XS, Huang HJ, Girod D et al (2015) Mitigation of tumor-associated fibroblast-facilitated head and neck cancer progression with anti-hepatocyte growth factor antibody Ficlatuzumab. JAMA Otolaryngol Head Neck Surg 141(12):1133–1139

    Article  PubMed  PubMed Central  Google Scholar 

  69. Zhou B, Chen WL, Wang YY, Lin ZY, Zhang DM, Fan S, Li JS (2014) A role for cancer-associated fibroblasts in inducing the epithelial-to-mesenchymal transition in human tongue squamous cell carcinoma. J Oral Pathol Med 43(8):585–592

    Article  CAS  PubMed  Google Scholar 

  70. Steinbichler TB, Metzler V, Pritz C, Riechelmann H, Dudas J (2016) Tumor-associated fibroblast-conditioned medium induces CDDP resistance in HNSCC cells. Oncotarget 7(3):2508–2518

    Article  PubMed  Google Scholar 

  71. Tan CT, Chu CY, Lu YC, Chang CC, Lin BR, Wu HH, Liu HL, Cha ST, Prakash E, Ko JY et al (2008) CXCL12/CXCR4 promotes laryngeal and hypopharyngeal squamous cell carcinoma metastasis through MMP-13-dependent invasion via the ERK1/2/AP-1 pathway. Carcinogenesis 29(8):1519–1527

    Article  CAS  PubMed  Google Scholar 

  72. Azad BB, Chatterjee S, Lesniak WG, Lisok A, Pullambhatla M, Bhujwalla ZM, Pomper MG, Nimmagadda S (2016) A fully human CXCR4 antibody demonstrates diagnostic utility and therapeutic efficacy in solid tumor xenografts. Oncotarget 7(11):12344–12358

    Article  PubMed  PubMed Central  Google Scholar 

  73. Seiwert TY, Burtness B, Mehra R, Weiss J, Berger R, Eder JP, Heath K, McClanahan T, Lunceford J, Gause C 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(7):956–965

    Article  CAS  PubMed  Google Scholar 

  74. Chow LQM, Haddad R, Gupta S, Mahipal A, Mehra R, Tahara M, Berger R, Eder JP, Burtness B, Lee SH et al (2016) Antitumor activity of Pembrolizumab in biomarker-unselected patients with recurrent and/or metastatic head and neck squamous cell carcinoma: results from the phase Ib KEYNOTE-012 expansion cohort. J Clin Oncol Off J Am Soc Clin Oncol 34(32):3838–3845

    Article  CAS  Google Scholar 

  75. Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington KJ, Kasper S, Vokes EE, Even C et al (2018) Nivolumab vs investigator's choice in recurrent or metastatic squamous cell carcinoma of the head and neck: 2-year long-term survival update of CheckMate 141 with analyses by tumor PD-L1 expression. Oral Oncol 81:45–51

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Harrington KJ, Ferris RL, Blumenschein G Jr, Colevas AD, Fayette J, Licitra L, Kasper S, Even C, Vokes EE, Worden F et al (2017) Nivolumab versus standard, single-agent therapy of investigator's choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): health-related quality-of-life results from a randomised, phase 3 trial. Lancet Oncol 18(8):1104–1115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Kiyota N, Hasegawa Y, Takahashi S, Yokota T, Yen CJ, Iwae S, Shimizu Y, Hong RL, Goto M, Kang JH et al (2017) A randomized, open-label, Phase III clinical trial of nivolumab vs. therapy of investigator's choice in recurrent squamous cell carcinoma of the head and neck: a subanalysis of Asian patients versus the global population in checkmate 141. Oral Oncol 73:138–146

    Article  CAS  PubMed  Google Scholar 

  78. Saba NF, Blumenschein G Jr, Guigay J, Licitra L, Fayette J, Harrington KJ, Kiyota N, Gillison ML, Ferris RL, Jayaprakash V et al (2019) Nivolumab versus investigator's choice in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: efficacy and safety in CheckMate 141 by age. Oral Oncol 96:7–14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Zandberg DP, Algazi AP, Jimeno A, Good JS, Fayette J, Bouganim N, Ready NE, Clement PM, Even C, Jang RW et al (2019) Durvalumab for recurrent or metastatic head and neck squamous cell carcinoma: results from a single-arm, phase II study in patients with >/=25% tumour cell PD-L1 expression who have progressed on platinum-based chemotherapy. Eur J Cancer (Oxford, England: 1990) 107:142–152

    Article  CAS  Google Scholar 

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Acknowledgment

Muzafar A. Macha is a recipient of Ramanujan Fellowship from Science & Engineering Research Board (SERB), Department of Science and Technology, Government of India, New Delhi.Mohammad Haris is supported by PI grant from Sidra Medicine (5071012001) and Ajaz A. Bhat is supported by Sidra Medicine Internal Research Fund (5011041002). 

Grant Support

Science & Engineering Research Board (SERB), Department of Science and Technology, Govt. of India, New Delhi.

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Authors and Affiliations

  1. Department of Biotechnology, Central University of Kashmir (CUK), Ganderbal, Jammu and Kashmir, India

    Muzafar A. Macha, Nissar A. Wani, Rais A. Ganai, Abid Hamid & Mohammad A. Zargar

  2. Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA

    Muzafar A. Macha & Surinder K. Batra

  3. Functional and Molecular Imaging Laboratory, Sidra Medicine, Doha, Qatar

    Ajaz A. Bhat, Sheema Hashem & Mohammad Haris

  4. Laboratory Animal Research Center, Qatar University, Doha, Qatar

    Mohammad Haris

  5. Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India

    Sham S. Chauhan

  6. Eppley Institute for Research in Cancer and Allied Diseases, Omaha, NE, USA

    Surinder K. Batra

  7. Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA

    Surinder K. Batra

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  1. Department of Radiology, Columbia University Medical Center, New York, NY, USA, Department of Pathology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Alexander Birbrair

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Macha, M.A. et al. (2020). Recent Advances in Head and Neck Tumor Microenvironment–Based Therapy. In: Birbrair, A. (eds) Tumor Microenvironments in Organs. Advances in Experimental Medicine and Biology, vol 1296. Springer, Cham. https://doi.org/10.1007/978-3-030-59038-3_2

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