Immune suppression in head and neck cancers: a review

Anaëlle Duray, Stéphanie Demoulin, Pascale Hubert, Philippe Delvenne, Sven Saussez, Anaëlle Duray, Stéphanie Demoulin, Pascale Hubert, Philippe Delvenne, Sven Saussez

Abstract

Head and neck squamous cell carcinomas (HNSCCs) are the sixth most common cancer in the world. Despite significant advances in the treatment modalities involving surgery, radiotherapy, and concomitant chemoradiotherapy, the 5-year survival rate remained below 50% for the past 30 years. The worse prognosis of these cancers must certainly be link to the fact that HNSCCs strongly influence the host immune system. We present a critical review of our understanding of the HNSCC escape to the antitumor immune response such as a downregulation of HLA class I and/or components of APM. Antitumor responses of HNSCC patients are compromised in the presence of functional defects or apoptosis of T-cells, both circulating and tumor-infiltrating. Langerhans cells are increased in the first steps of the carcinogenesis but decreased in invasive carcinomas. The accumulation of macrophages in the peritumoral areas seems to play a protumoral role by secreting VEGF and stimulating the neoangiogenesis.

Figures

Figure 1
Figure 1
Immunosuppressive mechanisms in the tumor microenvironment: several mechanisms are developed by cancerous cells to escape to the immune system such as a loss or a reduction of the expression of MHC class 1 molecules and costimulatory molecules, the expression of FasL to induce apoptosis of tumor-infiltrating lymphocytes and the production of immunosuppressive molecules such as TGF-β, PGE2, IL-6, IL-10, and adenosine. Among the subpopulations of naïve CD4+ T cells, CD4+ Th17 T cells promote inflammation by secreting IL-17 whereas CD4+ Th2 T cells promote antibody production by B cells. Tregs promote tumor progression by inhibiting the functions of CD4+ and CD8+ T cells and NK cells. TAMs M2 phenotype induce the expression of CD4+ Th2 T cell and Tregs. Moreover, M2 phenotype promote growth tumor (EGF, PDGF, TGF-β, IL-6, IL-1, and TNF-α), angiogenesis (TGF-β, VEGF, GM-CSF, TGF-α, IL-1, IL-6, and IL-8), invasion (MMPs, TNF-α, IL-1), immunosuppression (TGF-β, PGE2, and IL-10) and metastasis. MDSCs induce Treg, secrete IL-10, and inhibit CD4+ and CD8+ T cells.
Figure 2
Figure 2
Description of immunosuppressive mechanisms during the head and neck tumor progression: in the normal epithelia of the upper aerodigestive tracts, LCs are present in the suprabasal layers. When mucosae of these areas are exposed to tobacco, the number of LCs increases whereas these cells decrease in invasive carcinomas. The mature DCs are prominent in the peritumoral area and correlated positively with the expression of VEGF. DCs are also more abundant in patients with metastasis. A higher level of TAM is observed in HNSCCs, and these cells constitute a source of VEGF which play a crucial role in angiogenesis. HNSCCs can induce the apoptosis of CD8+ T cells using the mitochondrial and/or Fas/FasL pathways. Tregs can induce apoptosis of CD8+ T cells and inhibition of the proliferation of CD4+ T cells.

References

    1. Grandis JR, Pietenpol JA, Greenberger JS, Pelroy RA, Mohla S. Head and neck cancer: meeting summary and research opportunities. Cancer Research. 2004;64(21):8126–8129.
    1. Shah JP, Patel SG. Head and Neck Surgery and Oncology. New York, NY, USA: Mosby; 2003.
    1. Forastiere AA, Trotti A. Radiotherapy and concurrent chemotherapy: a strategy that improves locoregional control and survival in oropharyngeal cancer. Journal of the National Cancer Institute. 1999;91(24):2065–2066.
    1. Denis F, Garaud P, Bardet E, et al. Final results of the 94-01 French head and neck oncology and radiotherapy group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. Journal of Clinical Oncology. 2004;22(1):69–76.
    1. Adelstein DJ, Li Y, Adams GL, et al. An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. Journal of Clinical Oncology. 2003;21(1):92–98.
    1. Al-Sarraf M, LeBlanc M, Giri PGS, et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. Journal of Clinical Oncology. 1998;16(4):1310–1317.
    1. Jeremic B, Shibamoto Y, Milicic B, et al. Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial. Journal of Clinical Oncology. 2000;18(7):1458–1464.
    1. Cooper JS, Pajak TF, Forastiere AA, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. New England Journal of Medicine. 2004;350(19):1937–1944.
    1. Bernier J, Domenge C, Ozsahin M, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck advanced head and neck cancer. New England Journal of Medicine. 2004;350(19):1945–1952.
    1. Lang K, Menzin J, Earle CC, Jacobson J, Hsu MA. The economic cost of squamous cell cancer of the head and neck: findings from linked SEER-medicare data. Archives of Otolaryngology—Head and Neck Surgery. 2004;130(11):1269–1275.
    1. Swann JB, Smyth MJ. Immune surveillance of tumors. Journal of Clinical Investigation. 2007;117(5):1137–1146.
    1. Gorochov G, Papo T. Immunologie. Doin Groupe Liaisons; 2000.
    1. Costello RT, Gastaut JA, Olive D. Tumor escape from mmune surveillance. Archivum Immunologiae et Therapiae Experimentalis. 1999;47(2):83–88.
    1. Whiteside TL. Tumor-induced death of immune cells: its mechanisms and consequences. Seminars in Cancer Biology. 2002;12(1):43–50.
    1. Hoskin DW, Mader JS, Furlong SJ, Conrad DM, Blay J. Inhibition of T cell and natural killer cell function by adenosine and its contribution to immune evasion by tumor cells. International Journal of Oncology. 2008;32(3):527–535.
    1. Lewis CE, Pollard JW. Distinct role of macrophages in different tumor microenvironments. Cancer Research. 2006;66(2):605–612.
    1. Lamagna C, Aurrand-Lions M, Imhof BA. Dual role of macrophages in tumor growth and angiogenesis. Journal of Leukocyte Biology. 2006;80(4):705–713.
    1. Coffelt SB, Hughes R, Lewis CE. Tumor-associated macrophages: effectors of angiogenesis and tumor progression. Biochimica et Biophysica Acta. 2009;1796(1):11–18.
    1. Mantovani A, Schioppa T, Porta C, Allavena P, Sica A. Role of tumor-associated macrophages in tumor progression and invasion. Cancer and Metastasis Reviews. 2006;25(3):315–322.
    1. Sica A, Schioppa T, Mantovani A, Allavena P. Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. European Journal of Cancer. 2006;42(6):717–727.
    1. Condeelis J, Pollard JW. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell. 2006;124(2):263–266.
    1. Shih J-Y, Yuan A, Chen JJ-W, Yang P-C. Tumor-associated macrophages: its role in cancer invasion and metastasis. Journal of Cancer Molecules. 2006;2(3):101–106.
    1. Siveen KS, Kuttan G. Role of macrophages in tumour progression. Immunology Letters. 2009;123(2):97–102.
    1. Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell. 2010;141(1):39–51.
    1. Tsung K, Dolan JP, Tsung YL, Norton JA. Macrophages as effector cells in interleukin 12-induced T cell-dependent tumor rejection. Cancer Research. 2002;62(17):5069–5075.
    1. Brigati C, Noonan DM, Albini A, Benelli R. Tumors and inflammatory infiltrates: friends or foes? Clinical and Experimental Metastasis. 2002;19(3):247–258.
    1. Bingle L, Brown NJ, Lewis CE. The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. Journal of Pathology. 2002;196(3):254–265.
    1. Leek RD, Harris AL. Tumor-associated macrophages in breast cancer. Journal of Mammary Gland Biology and Neoplasia. 2002;7(2):177–189.
    1. Van Der Bij GJ, Oosterling SJ, Meijer S, Beelen RHJ, Van Egmond M. The role of macrophages in tumor development. Cellular Oncology. 2005;27(4):203–213.
    1. Ostrand-Rosenberg S. Immune surveillance: a balance between protumor and antitumor immunity. Current Opinion in Genetics and Development. 2008;18(1):11–18.
    1. Bi Y, Liu G, Yang R. Th17 cell induction and immune regulatory effects. Journal of Cellular Physiology. 2007;211(2):273–278.
    1. Viguier M, Lemaître F, Verola O, et al. Foxp3 expressing CD4+CD25high regulatory T cells are overrepresented in human metastatic melanoma lymph nodes and inhibit the function of infiltrating T cells. Journal of Immunology. 2004;173(2):1444–1453.
    1. Yang ZZ, Ansell SM. The role of T cells in the cancer immunological response. American Journal of Immunology. 2009;5(1):17–28.
    1. Curiel TJ, Coukos G, Zou L, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nature Medicine. 2004;10(9):942–949.
    1. Salama P, Phillips M, Grieu F, et al. Tumor-infiltrating Foxp3+ T regulatory cells show strong prognostic significance in colorectal cancer. Journal of Clinical Oncology. 2009;27(2):186–192.
    1. Huang B, Pan PY, Li Q, 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 Research. 2006;66(2):1123–1131.
    1. Sinha P, Clements VK, Bunt SK, Albelda SM, Ostrand-Rosenberg S. Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response. Journal of Immunology. 2007;179(2):977–983.
    1. Whiteside TL. Immunobiology of head and neck cancer. Cancer and Metastasis Reviews. 2005;24(1):95–105.
    1. Badoual C, Sandoval F, Pere H, et al. Better understanding tumor-host interaction in head and neck cancer to improve the design and development of immunotherapeutic strategies. Head and Neck. 2010;32(7):946–958.
    1. Young MRI. Protective mechanisms of head and neck squamous cell carcinomas from immune assault. Head and Neck. 2006;28(5):462–470.
    1. Ferris RL, Hunt JL, Ferrone S. Human leukocyte antigen (HLA) class I defects in head and neck cancer: molecular mechanisms and clinical significance. Immunologic Research. 2005;33(2):113–133.
    1. Albers A, Abe K, Hunt J, et al. Antitumor activity of human papillomavirus type 16 E7-specific T cells against virally infected squamous cell carcinoma of the head and neck. Cancer Research. 2005;65(23):11146–11155.
    1. López-Albaitero A, Nayak JV, Ogino T, et al. Role of antigen-processing machinery in the in vitro resistance of squamous cell carcinoma of the head and neck cells to recognition by CTL. Journal of Immunology. 2006;176(6):3402–3409.
    1. Hathaway B, Landsittel DP, Gooding W, et al. Multiplexed analysis of serum cytokines as biomarkers in squamous cell carcinoma of the head and neck patients. Laryngoscope. 2005;115(3):522–527.
    1. Hoffmann TK, Bier H, Whiteside TL. Targeting the immune system: novel therapeutic approaches in squamous cell carcinoma of the head and neck. Cancer Immunology, Immunotherapy. 2004;53(12):1055–1067.
    1. Reichert TE, Rabinowich H, Johnson JT, Whiteside TL. Mechanisms responsible for signaling and functional defects. Journal of Immunotherapy. 1998;21(4):295–306.
    1. Young MRI, Wright MA, Lozano Y, Matthews JP, Benefield J, Prechel MM. Mechanisms of immune suppression in patients with head and neck cancer: influence on the immune infiltrate of the cancer. International Journal of Cancer. 1996;67(3):333–338.
    1. Hoffmann TK, Dworacki G, Tsukihiro T, et al. Spontaneous apoptosis of circulating T lymphocytes in patients with head and neck cancer and its clinical importance. Clinical Cancer Research. 2002;8(8):2553–2562.
    1. Saito T, Kuss I, Dworacki G, Gooding W, Johnson JT, Whiteside TL. Spontaneous ex vivo apoptosis of peripheral blood mononuclear cells in patients with head and neck cancer. Clinical Cancer Research. 1999;5(6):1263–1273.
    1. Duffey DC, Chen Z, Dong G, et al. Expression of a dominant-negative mutant inhibitor-κBα of nuclear factor-κB in human head and neck squamous cell carcinoma inhibits survival, proinflammatory cytokine expression, and tumor growth in vivo. Cancer Research. 1999;59(14):3468–3474.
    1. Dasgupta S, Bhattacharya-Chatterjee M, O’Malley BW, Jr., Chatterjee SK. Recombinant vaccinia virus expressing interleukin-2 invokes anti-tumor cellular immunity in an orthotopic murine model of head and neck squamous cell carcinoma. Molecular Therapy. 2006;13(1):183–193.
    1. Saussez S, Camby I, Toubeau G, Kiss R. Galectins as modulators of tumor progression in head and neck squamous cell carcinomas. Head and Neck. 2007;29(9):874–884.
    1. Alhamarneh O, Amarnath SMP, Stafford ND, Greenman J. Regulatory T cells: what role do they play in antitumor immunity in patients with head and neck cancer? Head and Neck. 2008;30(2):251–261.
    1. Jewett A, Head C, Cacalano NA. Emerging mechanisms of immunosuppression in oral cancers. Journal of Dental Research. 2006;85(12):1061–1073.
    1. Kross KW, Heimdal JH, Aarstad HJ. Mononuclear phagocytes in head and neck squamous cell carcinoma. European Archives of Oto-Rhino-Laryngology. 2010;267(3):335–344.
    1. Antoniou AN, Powis SJ, Elliott T. Assembly and export of MHC class I peptide ligands. Current Opinion in Immunology. 2003;15(1):75–81.
    1. Ferris RL, Whiteside TL, Ferrone S. Immune escape associated with functional defects in antigen-processing machinery in head and neck cancer. Clinical Cancer Research. 2006;12(13):3890–3895.
    1. Ogino T, Shigyo H, Ishii H, et al. HLA class I antigen down-regulation in primary laryngeal squamous cell carcinoma lesions as a poor prognostic marker. Cancer Research. 2006;66(18):9281–9289.
    1. Grandis JR, Falkner DM, Melhem MF, Gooding WE, Drenning SD, Morel PA. Human leukocyte antigen class I allelic and haplotype loss in squamous cell carcinoma of the head and neck: clinical and immunogenetic consequences. Clinical Cancer Research. 2000;6(7):2794–2802.
    1. Tourkova IL, Shurin GV, Chatta GS, et al. Restoration by IL-15 of MHC class I antigen-processing machinery in human dendritic cells inhibited by tumor-derived gangliosides. Journal of Immunology. 2005;175(5):3045–3052.
    1. Steinbrink K, Mahnke K, Grabbe S, Enk AH, Jonuleit H. Myeloid dendritic cell: from sentinel of immunity to key player of peripheral tolerance? Human Immunology. 2009;70(5):289–293.
    1. Liu K, Nussenzweig MC. Origin and development of dendritic cells. Immunological Reviews. 2010;234(1):45–54.
    1. Valladeau J, Saeland S. Cutaneous dendritic cells. Seminars in Immunology. 2005;17(4):273–283.
    1. Charles J, Chaperot L, Salameire D, et al. Plasmacytoid dendritic cells and dermatological disorders: focus on their role in autoimmunity and cancer. European Journal of Dermatology. 2010;20(1):16–23.
    1. Cella M, Sallusto F, Lanzavecchia A. Origin, maturation and antigen presenting function of dendritic cells. Current Opinion in Immunology. 1997;9(1):10–16.
    1. Hawiger D, Inaba K, Dorsett Y, et al. Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. Journal of Experimental Medicine. 2001;194(6):769–779.
    1. Yamazaki S, Inaba K, Tarbell KV, Steinman RM. Dendritic cells expand antigen-specific Foxp3+CD25+CD4+ regulatory T cells including suppressors of alloreactivity. Immunological Reviews. 2006;212:314–329.
    1. Jonuleit H, Schmitt E, Schuler G, Knop J, Enk AH. Induction of interleukin 10-producing, nonproliferating CD4+ T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. Journal of Experimental Medicine. 2000;192(9):1213–1222.
    1. Barrett AW, Cruchley AT, Williams DM. Oral mucosal Langerhans’ cells. Critical Reviews in Oral Biology and Medicine. 1996;7(1):36–58.
    1. Cruchley AT, Williams DM, Farthing PM, Speight PM, Lesch CA, Squier CA. Langerhans cell density in normal human oral mucosa and skin: relationship to age, smoking and alcohol consumption. Journal of Oral Pathology and Medicine. 1994;23(2):55–59.
    1. Barett AW, Williams DM, Scott J. Effect of tobacco and alcohol consumption on the Langerhans cell population of human lingual epithelium determined using a monoclonal antibody against HLADR. Journal of Oral Pathology and Medicine. 1991;20(2):49–52.
    1. Daniels TE, Chou L, Greenspan JS, et al. Reduction of Langerhans cells in smokeless tobacco-associated oral mucosal lesions. Journal of Oral Pathology and Medicine. 1992;21(3):100–104.
    1. Boyle JO, Gümüş ZH, Kacker A, et al. Effects of cigarette smoke on the human oral mucosal transcriptome. Cancer Prevention Research. 2010;3(3):266–278.
    1. Girod SC, Kühnast T, Ulrich S, Krueger GRF. Langerhans cells in epithelial tumors and benign lesions of the oropharynx. In Vivo. 1994;8(4):543–547.
    1. Thompson AC, Griffin NR. Langerhans cells in normal and pathological vocal cord mucosa. Acta Oto-Laryngologica. 1995;115(6):830–832.
    1. Albuquerque RLC, Jr., Miguel MCC, Costa ALL, Souza LB. Correlation of c-erbB-2 and S-100 expression with the malignancy grading and anatomical site in oral squamous cell carcinoma. International Journal of Experimental Pathology. 2003;84(6):259–265.
    1. Yilmaz T, Gedikoglu G, Çelik A, Önerci M, Turan E. Prognostic significance of Langerhans cell infiltration in cancer of the larynx. Otolaryngology—Head and Neck Surgery. 2005;132(2):309–316.
    1. Ma CX, Jia TC, Li XR, Zhand ZF, Yiao CB. Langerhans cells in nasopharyngeal carcinoma in relation to prognosis. In Vivo. 1995;9(3):225–229.
    1. Gallo O, Libonati GA, Gallina E, et al. Langerhans cells related to prognosis in patients with laryngeal carcinoma. Archives of Otolaryngology—Head and Neck Surgery. 1991;117(9):1007–1010.
    1. Li X, Takahashi Y, Sakamoto K, Nakashima T. Expression of dendritic cell phenotypic antigens in cervical lymph nodes of patients with hypopharyngeal and laryngeal carcinoma. The Journal of Laryngology and Otology. Supplement. 2009;(31):5–10.
    1. Strauss L, Volland D, Kunkel M, Reichert TE. Dual role of VEGF family members in the pathogenesis of head and neck cancer (HNSCC): possible link between angiogenesis and immune tolerance. Medical Science Monitor. 2005;11(8):280–292.
    1. Kikuchi K, Kusama K, Sano M, et al. Vascular endothelial growth factor and dendritic cells in human squamous cell carcinoma of the oral cavity. Anticancer Research. 2006;26(3A):1833–1848.
    1. Kikuchi K, Kusama K, Taguchi K, et al. Dendritic cells in human squamous cell carcinoma of the oral cavity. Anticancer Research. 2002;22(2A):545–557.
    1. Wei N, Tahan SR. S100+ cell response to squamous cell carcinoma of the lip: inverse correlation with metastasis. Journal of Cutaneous Pathology. 1998;25(9):463–468.
    1. Pries R, Wulff S, Wollenberg B. Toll-like receptor modulation in head and neck cancer. Critical Reviews in Immunology. 2008;28(3):201–213.
    1. Frenzel H, Hoffmann B, Brocks C, Schlenke P, Pries R, Wollenberg B. Toll-like receptor interference in myeloid dendritic cells through head and neck cancer. Anticancer Research. 2006;26(6B):4409–4413.
    1. Hoffmann TK, Müller-Berghaus J, Ferris RL, Johnson JT, Storkus WJ, Whiteside TL. Alterations in the frequency of dendritic cell subsets in the peripheral circulation of patients with squamous cell carcinomas of the head and neck. Clinical Cancer Research. 2002;8(6):1787–1793.
    1. Colonna M, Trinchieri G, Liu YJ. Plasmacytoid dendritic cells in immunity. Nature Immunology. 2004;5(12):1219–1226.
    1. Hartmann E, Wollenberg B, Rothenfusser S, et al. Identification and functional analysis of tumor-infiltrating plasmacytoid dendritic cells in head and neck cancer. Cancer Research. 2003;63(19):6478–6487.
    1. Bekeredjian-Ding I, Schäfer M, Hartmann E, et al. Tumour-derived prostaglandin E and transforming growth factor-β synergize to inhibit plasmacytoid dendritic cell-derived interferon-α . Immunology. 2009;128(3):439–450.
    1. Auger MJ, Ross JA. The bilogy of macrophage. In: Lewis CE, McGee JO, editors. The Macrophage. Oxford, UK: Oxford University Press; 1992. pp. 2–74.
    1. Li C, Shintani S, Terakado N, Nakashiro KI, Hamakawa H. Infiltration of tumor-associated macrophages in human oral squamous cell carcinoma. Oncology Reports. 2002;9(6):1219–1223.
    1. Rittà M, De Andrea M, Mondini M, et al. Cell cycle and viral and immunologic profiles of head and neck squamous cell carcinoma as predictable variables of tumor progression. Head and Neck. 2009;31(3):318–327.
    1. Bárdos H, Juhász A, Répássy G, Ádány R. Fibrin deposition in squamous cell carcinomas of the larynx and hypopharynx. Thrombosis and Haemostasis. 1998;80(5):767–772.
    1. Salven P, Heikkilä P, Anttonen A, Kajanti M, Joensuu H. Vascular endothelial growth factor in squamous cell head and neck carcinoma: expression and prognostic significance. Modern Pathology. 1997;10(11):1128–1133.
    1. Neuchrist C, Quint C, Pammer A, Burian M. Vascular endothelial growth factor (VEGF) and microvessel density in squamous cell carcinomas of the larynx: an immunohistochemical study. Acta Oto-Laryngologica. 1999;119(6):732–738.
    1. Lalla RV, Boisoneau DS, Spiro JD, Kreutzer DL. Expression of vascular endothelial growth factor receptors on tumor cells in head and neck squamous cell carcinoma. Archives of Otolaryngology—Head and Neck Surgery. 2003;129(8):882–888.
    1. Liss C, Fekete MJ, Hasina R, Diemthuy Lam C, Lingen MW. Paracrine angiogenic loop between head-and-neck squamous-cell carcinomas and macrophages. International Journal of Cancer. 2001;93(6):781–785.
    1. Liu SY, Chang LC, Pan LF, Hung YJ, Lee CH, Shieh YS. Clinicopathologic significance of tumor cell-lined vessel and microenvironment in oral squamous cell carcinoma. Oral Oncology. 2008;44(3):277–285.
    1. Marcus B, Arenberg D, Lee J, et al. Prognostic factors in oral cavity and oropharyngeal squamous cell carcinoma: the impact of tumor-associated macrophages. Cancer. 2004;101(12):2779–2787.
    1. Abbas AK, Lichtman AH. Les Bases de L’immunologie Fondamentale et Clinique. Elsevier; 2005.
    1. Bergmann C, Strauss L, Zeidler R, Lang S, Whiteside TL. Expansion and characteristics of human T regulatory type 1 cells in co-cultures simulating tumor microenvironment. Cancer Immunology, Immunotherapy. 2007;56(9):1429–1442.
    1. Gastman BR, Atarashi Y, Reichert TE, et al. Fas ligand is expressed on human squamous cell carcinomas of the head and neck, and it promotes apoptosis of T lymphocytes. Cancer Research. 1999;59(20):5356–5364.
    1. Gastman BR, Johnson DE, Whiteside TL, Rabinowich H. Tumor-induced apoptosis of T lymphocytes: elucidation of intracellular apoptotic events. Blood. 2000;95(6):2015–2023.
    1. Gastman BR, Yin XM, Johnson DE, et al. Tumor-induced apoptosis of T cells: amplification by a mitochondrial cascade. Cancer Research. 2000;60(24):6811–6817.
    1. Kassouf N, Thornhill MH. Oral cancer cell lines can use multiple ligands, including Fas-L, TRAIL and TNF-α, to induce apoptosis in Jurkat T cells: possible mechanisms for immune escape by head and neck cancers. Oral Oncology. 2008;44(7):672–682.
    1. Bergmann C, Strauss L, Wieckowski E, et al. Tumor-derived microvesicles in sera of patients with head and neck cancer and their role in tumor progression. Head and Neck. 2009;31(3):371–380.
    1. Kim JW, Wieckowski E, Taylor DD, Reichert TE, Watkins S, Whiteside TL. Fas ligand-positive membranous vesicles isolated from sera of patients with oral cancer induce apoptosis of activated T lymphocytes. Clinical Cancer Research. 2005;11(3):1010–1020.
    1. Kim JW, Tsukishiro T, Johnson JT, Whiteside TL. Expression of pro- and antiapoptotic proteins in circulating CD8+ T cells of patients with squamous cell carcinoma of the head and neck. Clinical Cancer Research. 2004;10(15):5101–5110.
    1. Klatka J, Roliński J, Kupisz K, Klonowski S, Skomra D. Expression of bcl-2 protein in lymphocytes of patients with laryngeal carcinoma. European Archives of Oto-Rhino-Laryngology. 1999;256(6):299–302.
    1. Strauss L, Bergmann C, Whiteside TL. Human circulating CD4+CD25highFoxp3+ regulatory T cells kill autologous CD8+ but not CD4+ responder cells by Fas-mediated apoptosis. Journal of Immunology. 2009;182(3):1469–1480.
    1. Mandapathil M, Szczepanski MJ, Szajnik M, et al. Increased ectonucleotidase expression and activity in regulatory T cells of patients with head and neck cancer. Clinical Cancer Research. 2009;15(20):6348–6357.
    1. Bergmann C, Strauss L, Wang Y, et al. T regulatory type 1 cells in squamous cell carcinoma of the head and neck: mechanisms of suppression and expansion in advanced disease. Clinical Cancer Research. 2008;14(12):3706–3715.
    1. Badoual C, Hans S, Rodriguez J, et al. Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and neck cancers. Clinical Cancer Research. 2006;12(2):465–472.
    1. Zhang YL, Li J, Mo HY, et al. Different subsets of tumor infiltrating lymphocytes correlate with NPC progression in different ways. Molecular Cancer. 2010;9, article 4
    1. Loose D, Signore A, Bonanno E, et al. Prognostic value of CD25 expression on lymphocytes and tumor cells in squamous-cell carcinoma of the head and neck. Cancer Biotherapy and Radiopharmaceuticals. 2008;23(1):25–33.
    1. Strauss L, Bergmann C, Szczepanski M, Gooding W, Johnson JT, Whiteside TL. A unique subset of CD4+CD25high Foxp3+ T cells secreting interleukin-10 and transforming growth factor-β1 mediates suppression in the tumor microenvironment. Clinical Cancer Research. 2007;13(15):4345–4354.
    1. Gabriel A, Namysłowski G, Ziółkowski A, Morawski K, Steplewska-Mazur K, Urbaniec P. Immunohistochemical analysis of lymphocytic infiltration in the tumor microenvironment in patients operated on for laryngeal cancer. European Archives of Oto-Rhino-Laryngology. 1999;256(8):384–387.
    1. Whiteside TL. Down-regulation of ζ-chain expression in T cells: a biomarker of prognosis in cancer? Cancer Immunology, Immunotherapy. 2004;53(10):865–878.
    1. Reichert TE, Day R, Wagner EM, Whiteside TL. Absent or low expression of the ζ chain in T cells at the tumor site correlates with poor survival in patients with oral carcinoma. Cancer Research. 1998;58(23):5344–5347.
    1. Whiteside TL. Signaling defects in T lymphocytes of patients with malignancy. Cancer Immunology Immunotherapy. 1999;48(7):346–352.
    1. Kuss I, Saito T, Johnson JT, Whiteside TL. Clinical significance of decreased ζ chain expression in peripheral blood lymphocytes of patients with head and neck cancer. Clinical Cancer Research. 1999;5(2):329–334.
    1. Pignataro L, Pagani D, Brando B, Sambataro G, Scarpati B, Corsi MM. Down-regulation of ζ chain and zeta-associated protein 70 (Zap 70) expression in circulating T lymphocytes in laryngeal squamous cell carcinoma. Analytical and Quantitative Cytology and Histology. 2007;29(1):57–62.
    1. Reichert TE, Scheuer C, Day R, Wagner W, Whiteside TL. The number of intratumoral dendritic cells and ζ-chain expression in T cells as prognostic and survival biomarkers in patients with oral carcinoma. Cancer. 2001;91(11):2136–2147.
    1. Distel LV, Fickenscher R, Dietel K, et al. Tumour infiltrating lymphocytes in squamous cell carcinoma of the oro- and hypopharynx: prognostic impact may depend on type of treatment and stage of disease. Oral Oncology. 2009;45(10):e167–e174.
    1. Dorta RG, Landman G, Kowalski LP, Lauris JRP, Latorre MRDO, Oliveira DT. Tumour-associated tissue eosinophilia as a prognostic factor in oral squamous cell carcinomas. Histopathology. 2002;41(2):152–157.
    1. Goldsmith MM, Belchis DA, Cresson DH, Merritt WD, Askin FB. The importance of the eosinophil in head and neck cancer. Otolaryngology—Head and Neck Surgery. 1992;106(1):27–33.
    1. Horiuchi K, Mishima K, Ohsawa M, Sugimura M, Aozasa K. Prognostic factors for well-differentiated squamous cell carcinoma in the oral cavity with emphasis on immunohistochemical evaluation. Journal of Surgical Oncology. 1993;53(2):92–96.
    1. Said M, Wiseman S, Yang J, et al. Tissue eosinophilia: a morphologic marker for assessing stromal invasion in laryngeal squamous neoplasms. BMC Clinical Pathology. 2005;5, article 1
    1. Falconieri G, Luna MA, Pizzolitto S, DeMaglio G, Angione V, Rocco M. Eosinophil-rich squamous carcinoma of the oral cavity: a study of 13 cases and delineation of a possible new microscopic entity. Annals of Diagnostic Pathology. 2008;12(5):322–327.
    1. Tostes Oliveira D, Tjioe KC, Assao A, et al. Tissue eosinophilia and its association with tumoral invasion of oral cancer. International Journal of Surgical Pathology. 2009;17(3):244–249.
    1. Tadbir AA, Ashraf MJ, Sardari Y. Prognostic significance of stromal eosinophilic infiltration in oral squamous cell carcinoma. Journal of Craniofacial Surgery. 2009;20(2):287–289.
    1. Leighton SEJ, Teo JGC, Leung SF, Cheung AYK, Lee JCK, Van Hasselt CA. Prevalence and prognostic significance of tumor-associated tissue eosinophilia in nasopharyngeal carcinoma. Cancer. 1996;77(3):436–440.
    1. Manchanda P, Sharma SC, Das SN. Differential regulation of IL-2 and IL-4 in patients with tobacco-related oral squamous cell carcinoma. Oral Diseases. 2006;12(5):455–462.
    1. Riedel F, Adam S, Feick P, Haas S, Götte K, Hörmann K. Expression of IL-18 in patients with head and neck squamous cell carcinoma. International Journal of Molecular Medicine. 2004;13(2):267–272.
    1. Sparano A, Lathers DMR, Achille N, Petruzzelli GJ, Young MRI. Modulation of Th1 and Th2 cytokine profiles and their association with advanced head and neck squamous cell carcinoma. Otolaryngology—Head and Neck Surgery. 2004;131(5):573–576.
    1. Lau KM, Cheng SH, Lo KW, et al. Increase in circulating Foxp3+ CD4+CD25high regulatory T cells in nasopharyngeal carcinoma patients. British Journal of Cancer. 2007;96(4):617–622.
    1. Schaefer C, Kim GG, Albers A, Hoermann K, Myers EN, Whiteside TL. Characteristics of CD4+CD25+ regulatory T cells in the peripheral circulation of patients with head and neck cancer. British Journal of Cancer. 2005;92(5):913–920.
    1. Schwarz S, Butz M, Morsczeck C, Reichert TE, Driemel O. Increased number of CD25+Foxp3+ regulatory T cells in oral squamous cell carcinomas detected by chromogenic immunohistochemical double staining. Journal of Oral Pathology and Medicine. 2008;37(8):485–489.
    1. Strauss L, Bergmann C, Gooding W, Johnson JT, Whiteside TL. The frequency and suppressor function of CD4+CD25high Foxp3+ T cells in the circulation of patients with squamous cell carcinoma of the head and neck. Clinical Cancer Research. 2007;13(21):6301–6311.
    1. Dahlstrand H, Näsman A, Romanitan M, Lindquist D, Ramqvist T, Dalianis T. Human papillomavirus accounts both for increased incidence and better prognosis in tonsillar cancer. Anticancer Research. 2008;28(2B):1133–1138.
    1. Rosenquist K, Wennerberg J, Annertz K, et al. Recurrence in patients with oral and oropharyngeal squamous cell carcinoma: human papillomavirus and other risk factors. Acta Oto-Laryngologica. 2007;127(9):980–987.
    1. Lindel K, Beer KT, Laissue J, Greiner RH, Aebersold DM. Human papillomavirus positive squamous cell carcinoma of the oropharynx: a radiosensitive subgroup of head and neck carcinoma. Cancer. 2001;92(4):805–813.
    1. Lindquist D, Romanitan M, Hammarstedt L, et al. Human papillomavirus is a favourable prognostic factor in tonsillar cancer and its oncogenic role is supported by the expression of E6 and E7. Molecular Oncology. 2007;1(3):350–355.
    1. Fakhry C, Westra WH, Li S, et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. Journal of the National Cancer Institute. 2008;100(4):261–269.
    1. Weinberger PM, Yu Z, Haffty BG, et al. Molecular classification identifies a subset of human papillomavirus- associated oropharyngeal cancers with favorable prognosis. Journal of Clinical Oncology. 2006;24(5):736–747.
    1. Hennessey PT, Westra WH, Califano JA. Human papillomavirus and head and neck squamous cell carcinoma: recent evidence and clinical implications. Journal of Dental Research. 2009;88(4):300–306.
    1. Kumar B, Cordell KG, Lee JS, et al. EGFR, p16, HPV titer, Bcl-xL and p53, sex, and smoking as indicators of response to therapy and survival in oropharyngeal cancer. Journal of Clinical Oncology. 2008;26(19):3128–3137.
    1. Rosenquist K. Risk factors in oral and oropharyngeal squamous cell carcinoma: a population-based case-control study in southern Sweden. Swedish Dental Journal. Supplement. 2005;179:1–66.
    1. Hansson BG, Rosenquist K, Antonsson A, et al. Strong association between infection with human papillomavirus and oral and oropharyngeal squamous cell carcinoma: a population-based case-control study in southern Sweden. Acta Oto-Laryngologica. 2005;125(12):1337–1344.
    1. Morshed K. Association between human papillomavirus infection and laryngeal squamous cell carcinoma. Journal of Medical Virology. 2010;82(6):1017–1023.
    1. Bozdayi G, Kemaloglu Y, Ekinci O, et al. Role of human papillomavirus in the clinical and histopathologic features of laryngeal and hypopharyngeal cancers. Journal of Otolaryngology—Head and Neck Surgery. 2009;38(1):119–125.
    1. Yang SW, Lee YS, Chen TA, Wu CJ, Tsai CN. Human papillomavirus in oral leukoplakia is no prognostic indicator of malignant transformation. Cancer Epidemiology. 2009;33(2):118–122.
    1. Morshed K, Korobowicz E, Szymański M, Skomra D, Golabek W. Immunohistochemical demonstration of multiple HPV types in laryngeal squamous cell carcinoma. European Archives of Oto-Rhino-Laryngology. 2005;262(11):917–920.
    1. Aaltonen LM, Wahlström T, Rihkanen H, Vaheri A. A novel method to culture laryngeal human papillomavirus-positive epithelial cells produces papilloma-type cytology on collagen rafts. European Journal of Cancer. 1998;34(7):1111–1116.
    1. Ernoux-Neufcoeur P, Arafa M, Decaestecker C, et al. Combined analysis of HPV DNA, p16, p21 and p53 to predict prognosis in patients with stage IV hypopharyngeal carcinoma. Journal of Cancer Research and Clinical Oncology. 2010;137(1):173–181.
    1. Stanley MA. Immune responses to human papilloma viruses. Indian Journal of Medical Research. 2009;130(3):266–276.
    1. Albers A, Abe K, Hunt J, et al. Antitumor activity of human papillomavirus type 16 E7-specific T cells against virally infected squamous cell carcinoma of the head and neck. Cancer Research. 2005;65(23):11146–11155.
    1. Hoffmann TK, Arsov C, Schirlau K, et al. T cells specific for HPV16 E7 epitopes in patients with squamous cell carcinoma of the oropharynx. International Journal of Cancer. 2006;118(8):1984–1991.
    1. Williams R, Lee DW, Elzey BD, Anderson ME, Hostager BS, Lee JH. Preclinical models of HPV+ and HPV− HNSCC in mice: an immune clearance of HPV+ HNSCC. Head and Neck. 2009;31(7):911–918.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren