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Biological predictors of radiosensitivity in head and neck squamous cell carcinoma

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Abstract

Objectives

The aim of this study is to investigate the influence of prognostic biomarkers on radiosensitivity and survival of advanced head and neck squamous cell carcinomas treated by primary (chemo)radiation.

Material and methods

The clinicopathological data and immunohistochemical staining of p16, c-Met, survivin, PD-1, and PD-L1 of 82 primarily (chemo)irradiated patients with head and neck squamous cell carcinoma were analyzed. Associations with local and locoregional radiation response, overall survival (OS), disease-free (DFS), and disease-specific survival (DSS) were assessed.

Results

Complete tumor response was associated with increased patient age (p = 0.007), N0-status (p = 0.022), M0-status (p = 0.007), and p16-positivity (p = 0.022). High PD-L1 was associated with M0-status (p = 0.026) and indicated tumor response to irradiation (p = 0.057); survivin expression showed higher rates of response failure (p = 0.073). Low PD-1 was associated with increased T-stage (p = 0.029) and local recurrence (p = 0.014). High PD-1 was strongly correlated with PD-L1-positive tumor infiltrating lymphocytes (p < 0.001). Low PD-L1 showed a significant correlation with high c-Met expression (p = 0.01). Significant predictors for unfavorable univariate survival were incomplete tumor response (DSS, p < 0.001), single radiotherapy (DSS, p = 0.002), M1-status (DSS, p < 0.001), decreased radiation dose (DSS, p = 0.014), high survivin (DSS, p = 0.045), and high c-Met (OS, p < 0.05). Survivin and c-Met also showed prognostic significance in multivariate survival analysis.

Conclusions

P16 and PD-L1 indicate radiosensitivity, whereas survivin and c-Met implicate radioresistance in primarily (chemo)irradiated head and neck squamous cell carcinomas. The role of the PD-1/PD-L1 immune checkpoints in radiation response and survival merits further investigation.

Clinical relevance

The findings may improve patient-specific therapy according to individual tumor characteristics.

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References

  1. Haddad RI, Shin DM (2008) Recent advances in head and neck cancer. N Engl J Med 359:1143–1154. doi:10.1056/NEJMra0707975

    Article  PubMed  Google Scholar 

  2. D’Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, Westra WH, Gillison ML (2007) Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med 356:1944–1956

    Article  PubMed  Google Scholar 

  3. Akervall J, Nandalur S, Zhang J, Qian CN, Goldstein N, Gyllerup P, Gardinger Y, Alm J, Lorenc K, Nilsson K, Resau J, Wilson G, Teh B (2014) A novel panel of biomarkers predicts radioresistance in patients with squamous cell carcinoma of the head and neck. Eur J Cancer 50:570–581. doi:10.1016/j.ejca.2013.11.007

    Article  PubMed  Google Scholar 

  4. Argiris A, Karamouzis MV, Raben D, Ferris RL (2008) Head and neck cancer. Lancet 371:1695–1709. doi:10.1016/s0140-6736(08)60728-x

    Article  PubMed  Google Scholar 

  5. Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA, Pinto H, Forastiere A, Gillison ML (2008) Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst 100:261–269. doi:10.1093/jnci/djn011

    Article  PubMed  Google Scholar 

  6. Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman C, Redmond KP, Gillison ML (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363:24–35. doi:10.1056/NEJMoa0912217

    Article  PubMed  PubMed Central  Google Scholar 

  7. Bhardwaj V, Cascone T, Cortez MA, Amini A, Evans J, Komaki RU, Heymach JV, Welsh JW (2013) Modulation of c-Met signaling and cellular sensitivity to radiation: potential implications for therapy. Cancer 119:1768–1775. doi:10.1002/cncr.27965

    Article  PubMed  PubMed Central  Google Scholar 

  8. Peruzzi B, Bottaro DP (2006) Targeting the c-Met signaling pathway in cancer. Clin Cancer Res 12:3657–3660. doi:10.1158/1078-0432.CCR-06-0818

    Article  PubMed  Google Scholar 

  9. Blumenschein GR Jr, Mills GB, Gonzalez-Angulo AM (2012) Targeting the hepatocyte growth factor-cMET axis in cancer therapy. J Clin Oncol 30:3287–3296. doi:10.1200/JCO.2011.40.3774

    Article  PubMed  PubMed Central  Google Scholar 

  10. Seiwert TY, Jagadeeswaran R, Faoro L, Janamanchi V, Nallasura V, El Dinali M, Yala S, Kanteti R, Cohen EE, Lingen MW, Martin L, Krishnaswamy S, Klein-Szanto A, Christensen JG, Vokes EE, Salgia R (2009) The MET receptor tyrosine kinase is a potential novel therapeutic target for head and neck squamous cell carcinoma. Cancer Res 69:3021–3031. doi:10.1158/0008-5472.CAN-08-2881

    Article  PubMed  PubMed Central  Google Scholar 

  11. Baschnagel AM, Williams L, Hanna A, Chen PY, Krauss DJ, Pruetz BL, Akervall J, Wilson GD (2014) c-Met expression is a marker of poor prognosis in patients with locally advanced head and neck squamous cell carcinoma treated with chemoradiation. Int J Radiat Oncol Biol Phys 88:701–707. doi:10.1016/j.ijrobp.2013.11.013

    Article  PubMed  Google Scholar 

  12. Ettl T, Viale-Bouroncle S, Hautmann M, Gosau M, Kölbl O, Reichert TE, Morsczeck C (2015) AKT and MET signalling mediates antiapoptotic radioresistance in head neck cancer cell lines. Oral Oncol 51:158–163. doi:10.1016/j.oraloncology.2014.11.005

    Article  PubMed  Google Scholar 

  13. De Bacco F, Luraghi P, Medico E, Reato G, Girolami F, Perera T, Gabriele P, Comoglio PM, Boccaccio C (2011) Induction of MET by ionizing radiation and its role in radioresistance and invasive growth of cancer. J Natl Cancer Inst 103:645–661. doi:10.1093/jnci/djr093

    Article  PubMed  Google Scholar 

  14. Lippert BM, Knauer SK, Fetz V, Mann W, Stauber RH (2007) Dynamic survivin in head and neck cancer: molecular mechanism and therapeutic potential. Int J Cancer 121:1169–1174. doi:10.1002/ijc.22941

    Article  PubMed  Google Scholar 

  15. Kim BM, Hong Y, Lee S, Liu P, Lim JH, Lee YH, Lee TH, Chang KT, Hong Y (2015) Therapeutic implications for overcoming radiation resistance in cancer therapy. Int J Mol Sci 16:26880–26913. doi:10.3390/ijms161125991

    Article  PubMed  PubMed Central  Google Scholar 

  16. Cheung CH, Huang CC, Tsai FY, Lee JY, Cheng SM, Chang YC, Huang YC, Chen SH, Chang JY (2013) Survivin—biology and potential as a therapeutic target in oncology. Onco Targets Ther 6:1453–1462. doi:10.2147/OTT.S33374

    Article  PubMed  PubMed Central  Google Scholar 

  17. Ambrosini G, Adida C, Altieri DC (1997) A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 3:917–921

    Article  PubMed  Google Scholar 

  18. Freier K, Pungs S, Sticht C, Flechtenmacher C, Lichter P, Joos S, Hofele C (2007) High survivin expression is associated with favorable outcome in advanced primary oral squamous cell carcinoma after radiation therapy. Int J Cancer 120:942–946. doi:10.1002/ijc.22380

    Article  PubMed  Google Scholar 

  19. Farnebo L, Tiefenböck K, Ansell A, Thunell LK, Garvin S, Roberg K (2013) Strong expression of survivin is associated with positive response to radiotherapy and improved overall survival in head and neck squamous cell carcinoma patients. Int J Cancer 133:1994–2003. doi:10.1002/ijc.28200

    Article  PubMed  Google Scholar 

  20. Schoenfeld JD (2015) Immunity in head and neck cancer. Cancer Immunol Res 3:12–17. doi:10.1158/2326-6066.CIR-14-0205

    Article  PubMed  Google Scholar 

  21. Chen L (2004) Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat Rev Immunol 4:336–347. doi:10.1038/nri1349

    Article  PubMed  Google Scholar 

  22. D’Incecco A, Andreozzi M, Ludovini V, Rossi E, Capodanno A, Landi L, Tibaldi C, Minuti G, Salvini J, Coppi E, Chella A, Fontanini G, Filice ME, Tornillo L, Incensati RM, Sani S, Crino L, Terracciano L, Cappuzzo F (2015) PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients. Br J Cancer 112:95–102. doi:10.1038/bjc.2014.555

    Article  PubMed  Google Scholar 

  23. Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, Lennon VA, Celis E, Chen L (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 8:793–800. doi:10.1038/nm730

    Article  PubMed  Google Scholar 

  24. Zou W, Chen L (2008) Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol 8:467–477. doi:10.1038/nri2326

    Article  PubMed  Google Scholar 

  25. Taube JM, Anders RA, Young GD, Xu H, Sharma R, McMiller TL, Chen S, Klein AP, Pardoll DM, Topalian SL, Chen L (2012) Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med 4:127ra137. doi:10.1126/scitranslmed.3003689

    Article  Google Scholar 

  26. Eppihimer MJ, Gunn J, Freeman GJ, Greenfield EA, Chernova T, Erickson J, Leonard JP (2002) Expression and regulation of the PD-L1 immunoinhibitory molecule on microvascular endothelial cells. Microcirculation 9:133–145. doi:10.1038/sj/mn/7800123

    Article  PubMed  PubMed Central  Google Scholar 

  27. Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC, Horton HF, Fouser L, Carter L, Ling V, Bowman MR, Carreno BM, Collins M, Wood CR, Honjo T (2000) Engagment of PD-1 the immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 192:1027–1034

    Article  PubMed  PubMed Central  Google Scholar 

  28. Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N (2002) Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci U S A 99:12293–12297. doi:10.1073/pnas.192461099

    Article  PubMed  PubMed Central  Google Scholar 

  29. Dovedi SJ, Adlard AL, Lipowska-Bhalla G, McKenna C, Jones S, Cheadle EJ, Stratford IJ, Poon E, Morrow M, Stewart R, Jones H, Wilkinson RW, Honeychurch J, Illidge TM (2014) Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade. Cancer Res 74:5458–5468. doi:10.1158/0008-5472.CAN-14-1258

    Article  PubMed  Google Scholar 

  30. Zeng J, See AP, Phallen J, Jackson CM, Belcaid Z, Ruzevick J, Durham N, Meyer C, Harris TJ, Albesiano E, Pradilla G, Ford E, Wong J, Hammers HJ, Mathios D, Tyler B, Brem H, Tran PT, Pardoll D, Drake CG, Lim M (2013) Anti-PD-1 blockade and stereotactic radiation produce long-term survival in mice with intracranial gliomas. Int J Radiat Oncol Biol Phys 86:343–349. doi:10.1016/j.ijrobp.2012.12.025

    Article  PubMed  PubMed Central  Google Scholar 

  31. Verbrugge I, Hagekyriakou J, Sharp LL, Galli M, West A, McLaughlin NM, Duret H, Yagita H, Johnstone RW, Smyth MJ, Haynes NM (2012) Radiotherapy increases the permissiveness of established mammary tumors to rejection by immunomodulatory antibodies. Cancer Res 72:3163–3174. doi:10.1158/0008-5472.CAN-12-0210

    Article  PubMed  Google Scholar 

  32. Vokes EE, Liebowitz DN, Weichselbaum RR (1997) Nasopharyngeal carcinoma. Lancet 350:1087–1091. doi:10.1016/s0140-6736(97)07269-3

    Article  PubMed  Google Scholar 

  33. Pignon JP, le Maitre A, Bourhis J, Group M-NC (2007) Meta-analyses of chemotherapy in head and neck cancer (MACH-NC): an update. Int J Radiat Oncol Biol Phys 69:S112–S114. doi:10.1016/j.ijrobp.2007.04.088

    Article  PubMed  Google Scholar 

  34. Milanes-Yearsley M, Hammond ME, Pajak TF, Cooper JS, Chang C, Griffin T, Nelson D, Laramore G, Pilepich M (2002) Tissue micro-array: a cost and time-effective method for correlative studies by regional and national cancer study groups. Mod Pathol 15:1366–1373. doi:10.1097/01.MP.0000036345.18944.22

    Article  PubMed  Google Scholar 

  35. Heiduschka G, Grah A, Oberndorfer F, Kadletz L, Altorjai G, Kornek G, Wrba F, Thurnher D, Selzer E (2015) Improved survival in HPV/p16-positive oropharyngeal cancer patients treated with postoperative radiotherapy. Strahlenther Onkol 191:209–216. doi:10.1007/s00066-014-0753-7

    Article  PubMed  Google Scholar 

  36. Laurent-Puig P, Cayre A, Manceau G, Buc E, Bachet JB, Lecomte T, Rougier P, Lievre A, Landi B, Boige V, Ducreux M, Ychou M, Bibeau F, Bouche O, Reid J, Stone S, Penault-Llorca F (2009) Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer. J Clin Oncol 27:5924–5930. doi:10.1200/JCO.2008.21.6796

    Article  PubMed  Google Scholar 

  37. Tsuta K, Kozu Y, Mimae T, Yoshida A, Kohno T, Sekine I, Tamura T, Asamura H, Furuta K, Tsuda H (2012) c-MET/phospho-MET protein expression and MET gene copy number in non-small cell lung carcinomas. J Thorac Oncol 7:331–339

    Article  PubMed  Google Scholar 

  38. Böger C, Behrens H-M, Mathiak M, Krüger S, Kalthoff H, Röcken C (2016) PD-L1 is an independent prognostic predictor in gastric cancer of western patients. Oncotarget 7:24269–24283

    Article  PubMed  PubMed Central  Google Scholar 

  39. Lassen P, Eriksen JG, Hamilton-Dutoit S, Tramm T, Alsner J, Overgaard J (2009) Effect of HPV-associated p16INK4A expression on response to radiotherapy and survival in squamous cell carcinoma of the head and neck. J Clin Oncol 27:1992–1998. doi:10.1200/JCO.2008.20.2853

    Article  PubMed  Google Scholar 

  40. Nakao Y, Yang X, Yokoyama M, Ferenczy A, Tang S-C, Pater MM, Pater A (1997) Induction of p16 during immortalization by HPV 16 and 18 and not during malignant transformation. Br J Cancer 75:1410–1416

    Article  PubMed  PubMed Central  Google Scholar 

  41. Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L, Zahurak ML, Daniel RW, Viglione M, Symer DE, Shah KV, Sidransky D (2000) Evidence for a causal association between human Papillomvirus and a subset of head and neck cancer. J Natl Cancer Inst 92:709–720

    Article  PubMed  Google Scholar 

  42. Chen X, Duan N, Zhang C, Zhang W (2016) Survivin and tumorigenesis: molecular mechanisms and therapeutic strategies. J Cancer 7:314–323. doi:10.7150/jca.13332

    Article  PubMed  PubMed Central  Google Scholar 

  43. Capalbo G, Rödel C, Stauber RH, Knauer SK, Bache M, Kappler M, Rödel F (2007) The role of survivin for radiation therapy. Prognostic and predictive factor and therapeutic target. Strahlenther Onkol 183:593–599. doi:10.1007/s00066-007-1800-4

    Article  PubMed  Google Scholar 

  44. Erpolat OP, Gocun PU, Akmansu M, Karakus E, Akyol G (2012) High expression of nuclear survivin and aurora B predicts poor overall survival in patients with head and neck squamous cell cancer. Strahlenther Onkol 188:248–254. doi:10.1007/s00066-011-0042-7

    Article  PubMed  Google Scholar 

  45. Lo Muzio L, Pannone G, Staibano S, Mignogna MD, Rubini C, Mariggio MA, Procaccini M, Ferrari F, De Rosa G, Altieri DC (2003) Survivin expression in oral squamous cell carcinoma. Br J Cancer 89:2244–2248. doi:10.1038/sj.bjc.6601402

    Article  PubMed  Google Scholar 

  46. Li F, Yang J, Ramnath N, Javle MM, Tan D (2005) Nuclear or cytoplasmic expression of survivin: what is the significance? Int J Cancer 114:509–512. doi:10.1002/ijc.20768

    Article  PubMed  PubMed Central  Google Scholar 

  47. Fan S, Ma XY, Wang JA, Yuan RQ, Meng Q, Cao Y, Laterra JJ, Goldberg ID, Rosen EM (2000) The cytokine hepatocyte growth factor/scatter factor inhibits apoptosis and enhances DNA repair by a common mechanism involving signaling through phosphatidyl inositol 3′ kinase. Oncogene 19:2212–2223

    Article  PubMed  Google Scholar 

  48. Zhang YW, Vande Woude GF (2003) HGF/SF-met signaling in the control of branching morphogenesis and invasion. J Cell Biochem 88:408–417. doi:10.1002/jcb.10358

    Article  PubMed  Google Scholar 

  49. Su L, Wang Y, Xiao M, Lin Y, Yu L (2010) Up-regulation of survivin in oral squamous cell carcinoma correlates with poor prognosis and chemoresistance. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 110:484–491. doi:10.1016/j.tripleo.2010.04.009

    Article  PubMed  Google Scholar 

  50. Tang MKS, Zhou HY, Yam JWP, Wong AST (2010) c-Met overexpression contributes to the acquired apoptotic resistance of Nonadherent ovarian cancer cells through a cross talk mediated by phosphatidylinositol 3-kinase and extracellular signal-regulated kinase 1/2. Neoplasia 12:128–IN125. doi:10.1593/neo.91438

    Article  PubMed  PubMed Central  Google Scholar 

  51. Zandberg DP, Strome SE (2014) The role of the PD-L1:PD-1 pathway in squamous cell carcinoma of the head and neck. Oral Oncol 50:627–632. doi:10.1016/j.oraloncology.2014.04.003

    Article  PubMed  Google Scholar 

  52. Vassilakopoulou M, Avgeris M, Velcheti V, Kotoula V, Rampias T, Chatzopoulos K, Perisanidis C, Kontos CK, Giotakis AI, Scorilas A, Rimm D, Sasaki C, Fountzilas G, Psyrri A (2016) Evaluation of PD-L1 expression and associated tumor-infiltrating lymphocytes in laryngeal squamous cell carcinoma. Clin Cancer Res 22:704–713. doi:10.1158/1078-0432.CCR-15-1543

    Article  PubMed  Google Scholar 

  53. Pardoll DM (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12:252–264. doi:10.1038/nrc3239

    Article  PubMed  PubMed Central  Google Scholar 

  54. Wu CT, Chen WC, Chang YH, Lin WY, Chen MF (2016) The role of PD-L1 in the radiation response and clinical outcome for bladder cancer. Sci Rep 6:19740–19749. doi:10.1038/srep19740

    Article  PubMed  PubMed Central  Google Scholar 

  55. Lin YM, Sung WW, Hsieh MJ, Tsai SC, Lai HW, Yang SM, Shen KH, Chen MK, Lee H, Yeh KT, Chen CJ (2015) High PD-L1 expression correlates with metastasis and poor prognosis in oral squamous cell carcinoma. PLoS One 10:e0142656. doi:10.1371/journal.pone.0142656

    Article  PubMed  PubMed Central  Google Scholar 

  56. Balan M, Miery Teran E, Waaga-Gasser AM, Gasser M, Choueiri TK, Freeman G, Pal S (2015) Novel roles of c-Met in the survival of renal cancer cells through the regulation of HO-1 and PD-L1 expression. J Biol Chem 290:8110–8120. doi:10.1074/jbc.M114.612689

    Article  PubMed  PubMed Central  Google Scholar 

  57. Taube JM, Klein A, Brahmer JR, Xu H, Pan X, Kim JH, Chen L, Pardoll DM, Topalian SL, Anders RA (2014) Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res 20:5064–5074. doi:10.1158/1078-0432.CCR-13-3271

    Article  PubMed  PubMed Central  Google Scholar 

  58. Salama AK, Postow MA, Salama JK (2016) Irradiation and immunotherapy: from concept to the clinic. Cancer 122:1659–1671. doi:10.1002/cncr.29889

    Article  PubMed  Google Scholar 

  59. Seiwert TY, Burtness B, Mehra R, Weiss J, Berger R, Eder JP, Heath K, McClanahan T, Lunceford J, Gause C, Cheng JD, Chow LQ (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. doi:10.1016/s1470-2045(16)30066-3

    Article  PubMed  Google Scholar 

  60. Topalian S, Hodi F, Brahmer J, Gettinger S, Smith D, McDermott D, Powderly J, Carvajal R, Sosman J, Atkins M, Leming P, Spigel D, Antonia S, Horn L, Drake C, Pardoll D, Chen L, Sharfman W, Anders R, Taube J, McMiller T, Xu H, Korman A, Jure-Kunkel M, Agrawal S, McDonald D, Kollia G, Gupta A, Wigginton J, Sznol M (2012) Safety, activity, and immune correlates of anti–PD-1 antibody in cancer. N Engl J Med 366:2443–2454. doi:10.1056/NEJMoa1200690

    Article  PubMed  PubMed Central  Google Scholar 

  61. Sharabi AB, Lim M, DeWeese TL, Drake CG (2015) Radiation and checkpoint blockade immunotherapy: radiosensitisation and potential mechanisms of synergy. Lancet Oncol 16:e498–e509. doi:10.1016/s1470-2045(15)00007-8

    Article  PubMed  Google Scholar 

  62. Twyman-Saint Victor C, Rech AJ, Maity A, Rengan R, Pauken KE, Stelekati E, Benci JL, Xu B, Dada H, Odorizzi PM, Herati RS, Mansfield KD, Patsch D, Amaravadi RK, Schuchter LM, Ishwaran H, Mick R, Pryma DA, Xu X, Feldman MD, Gangadhar TC, Hahn SM, Wherry EJ, Vonderheide RH, Minn AJ (2015) Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature 520:373–377. doi:10.1038/nature14292

    Article  PubMed  Google Scholar 

  63. Weiner LM, Surana R, Wang S (2010) Monoclonal antibodies: versatile platforms for cancer immunotherapy. Nat Rev Immunol 10:317–327. doi:10.1038/nri2744

    Article  PubMed  PubMed Central  Google Scholar 

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  1. Mathias Fiedler and Florian Weber both authors contributed equally to the results of this work

Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany

    Mathias Fiedler, Torsten E. Reichert, Christoph Klingelhöffer, Johannes K. Meier & Tobias Ettl

  2. Institute of Pathology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany

    Florian Weber

  3. Department of Radiotherapy, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany

    Matthias G. Hautmann

  4. Department of Otorhinolaryngology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany

    Frank Haubner

  5. Department of Dermatology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany

    Stephan Schreml

  6. Institute of Pathology, University Hospital of Erlangen, Krankenhausstraße 8/10, 91054, Erlangen, Germany

    Arndt Hartmann

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The work was supported by the Department of Oral and Maxillofacial Surgery and the Institute of Pathology of the University Hospital Regensburg, Germany.

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The study was approved by the Ethics Committee of the University of Regensburg (Nr. 15-101-0336) and have been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Fiedler, M., Weber, F., Hautmann, M.G. et al. Biological predictors of radiosensitivity in head and neck squamous cell carcinoma. Clin Oral Invest 22, 189–200 (2018). https://doi.org/10.1007/s00784-017-2099-x

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