Skip to main content

Advertisement

SpringerLink
Log in

Novel Insights of Anti-EGFR Therapy in HNSCC: Combined with Immunotherapy or Not?

  • HEAD AND NECK CANCERS (EY HANNA, SECTION EDITOR)
  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The efficacy of anti-EGFR therapy is still unfavorable in recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) patients. Disorder of antitumor immunity and aberrantly expressed checkpoint biomarkers had been validated to involve anti-EGFR therapy tolerance and efficacy. Here we review the immunomodulation of anti-EGFR therapy in the tumor immune microenvironment (TIME) of HNSCC and assist clinicians in finding the potential strategies to rescue anti-EGFR tolerance therapy in the era of immunotherapy for HNSCC.

Recent Findings

Anti-EGFR therapy, especially cetuximab, was validated to induce the innate and adaptive immune responses of HNSCC patients. It is mainly through inducing natural killer (NK) cells mediating antibody-dependent cell-mediated cytotoxicity (ADCC), recruiting multiple tumor-infiltrating immune cells, and finally remodeling the TIME. Moreover, mountains of preclinical models and clinical trials revealed that combining anti-EGFR agents with immunotherapy could enhance the antitumor effectiveness in HNSCC. Anti-EGFR therapy may usher in another dawn in the treatment of patients with HNSCC through combination with immunotherapy.

Summary

We offer an overview of the ongoing efforts to make out the immunomodulation of the EGFR pathway in both innate and adaptive immune responses; update the constant preclinical models and clinical trials for the combination of anti-EGFR and immunotherapy in HNSCC; and finally evaluate the efficacy and advantages of the combination therapeutic strategies in clinical use.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. •• Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, et al. Head and neck squamous cell carcinoma. Nat Rev Dis Primers. 2020;6(1): 92. https://doi.org/10.1038/s41572-020-00224-3This review integrates the biology and immunobiology of HNSCC to identify predictive biomarkers that will make better management for patients with HNSCC.

  2. Leonard B, Brand TM, O’Keefe RA, Lee ED, Zeng Y, et al. BET inhibition overcomes receptor tyrosine kinase-mediated cetuximab resistance in HNSCC. Cancer Res. 2018;78(15):4331–43.

    Article  CAS  Google Scholar 

  3. Xu MJ, Johnson DE, Grandis JR. EGFR-targeted therapies in the post-genomic era. Cancer Metastasis Rev. 2017;36(3):463–73. https://doi.org/10.1007/s10555-017-9687-8.

    Article  Google Scholar 

  4. Mazorra Z, Lavastida A, Concha-Benavente F, Valdés A, Srivastava RM, et al. Nimotuzumab induces NK cell activation, cytotoxicity, dendritic cell maturation and expansion of EGFR-specific T cells in head and neck cancer patients. Front Pharmacol. 2017;8:382. https://doi.org/10.3389/fphar.2017.00382.

    Article  CAS  Google Scholar 

  5. Cramer JD, Burtness B, Le QT, Ferris RL. The changing therapeutic landscape of head and neck cancer. Nat Rev Clin Oncol. 2019;16(11):669–83. https://doi.org/10.1038/s41571-019-0227-z.

    Article  Google Scholar 

  6. Fasano M, Della Corte CM, Viscardi G, Di Liello R, Paragliola F, et al. Head and neck cancer: the role of anti-EGFR agents in the era of immunotherapy. Ther Adv Med Oncol. 2021;13:1758835920949418. https://doi.org/10.1177/1758835920949418.

    Article  CAS  Google Scholar 

  7. Kumagai S, Koyama S, Nishikawa H. Antitumour immunity regulated by aberrant ERBB family signalling. Nat Rev Cancer. 2021;21(3):181–97. https://doi.org/10.1038/s41568-020-00322-0.

    Article  CAS  Google Scholar 

  8. Chung CH, Germain A, Subramaniam RM, Heilmann AM, Fedorchak K, et al. Genomic alterations in human epidermal growth factor receptor 2 (HER2/ERBB2) in head and neck squamous cell carcinoma. Head Neck. 2017;39(1):E15-e9. https://doi.org/10.1002/hed.24587.

    Article  Google Scholar 

  9. Alsahafi E, Begg K, Amelio I, Raulf N, Lucarelli P, et al. Clinical update on head and neck cancer: molecular biology and ongoing challenges. Cell Death Dis. 2019;10(8):540. https://doi.org/10.1038/s41419-019-1769-9.

    Article  Google Scholar 

  10. Ozanne B, Richards CS, Hendler F, Burns D, Gusterson B. Over-expression of the EGF receptor is a hallmark of squamous cell carcinomas. J Pathol. 1986;149(1):9–14. https://doi.org/10.1002/path.1711490104.

    Article  CAS  Google Scholar 

  11. • Guo Y, Luo Y, Zhang Q, Huang X, Li Z, et al. First-line treatment with chemotherapy plus cetuximab in Chinese patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: efficacy and safety results of the randomised, phase III CHANGE-2 trial. Eur J Cancer. 2021;156: 35–45. https://doi.org/10.1016/j.ejca.2021.06.039.This clinical trial demonstrates the effectiveness of combined cetuximab with a modified chemotherapy regimen. The result showed that Chinese patients with R/M HNSCC had an improved prognosis with the combination therapy above.

  12. Arnold L, Enders J, Thomas SM. Activated HGF-c-Met axis in head and neck cancer. Cancers (Basel). 2017;9(12):169. https://doi.org/10.3390/cancers9120169

  13. Madoz-Gúrpide J, Zazo S, Chamizo C, Casado V, Caramés C, et al. Activation of MET pathway predicts poor outcome to cetuximab in patients with recurrent or metastatic head and neck cancer. J Transl Med. 2015;13:282. https://doi.org/10.1186/s12967-015-0633-7.

    Article  CAS  Google Scholar 

  14. Wu X, Cheng YL, Matthen M, Yoon A, Schwartz GK, et al. Down-regulation of the tumor suppressor miR-34a contributes to head and neck cancer by up-regulating the MET oncogene and modulating tumor immune evasion. J Exp Clin Cancer Res. 2021;40(1):70. https://doi.org/10.1186/s13046-021-01865-2.

    Article  CAS  Google Scholar 

  15. Geiger JL, Grandis JR, Bauman JE. The STAT3 pathway as a therapeutic target in head and neck cancer: barriers and innovations. Oral Oncol. 2016;56:84–92. https://doi.org/10.1016/j.oraloncology.2015.11.022.

    Article  CAS  Google Scholar 

  16. Bu LL, Yu GT, Wu L, Mao L, Deng WW, et al. STAT3 induces immunosuppression by upregulating PD-1/PD-L1 in HNSCC. J Dent Res. 2017;96(9):1027–34. https://doi.org/10.1177/0022034517712435.

    Article  CAS  Google Scholar 

  17. Monteverde M, Milano G, Strola G, Maffi M, Lattanzio L, et al. The relevance of ADCC for EGFR targeting: a review of the literature and a clinically-applicable method of assessment in patients. Crit Rev Oncol Hematol. 2015;95(2):179–90. https://doi.org/10.1016/j.critrevonc.2015.02.014.

    Article  Google Scholar 

  18. Srivastava RM, Lee SC, Andrade Filho PA, Lord CA, Jie HB, et al. Cetuximab-activated natural killer and dendritic cells collaborate to trigger tumor antigen-specific T-cell immunity in head and neck cancer patients. Clin Cancer Res. 2013;19(7):1858–72. https://doi.org/10.1158/1078-0432.Ccr-12-2426.

    Article  CAS  Google Scholar 

  19. Jie HB, Schuler PJ, Lee SC, Srivastava RM, Argiris A, et al. CTLA-4+ regulatory T cells increased in cetuximab-treated head and neck cancer patients suppress NK cell cytotoxicity and correlate with poor prognosis. Cancer Res. 2015;75(11):2200–10. https://doi.org/10.1158/0008-5472.Can-14-2788.

    Article  CAS  Google Scholar 

  20. Trivedi S, Srivastava RM, Concha-Benavente F, Ferrone S, Garcia-Bates TM, et al. Anti-EGFR targeted monoclonal antibody isotype influences antitumor cellular immunity in head and neck cancer patients. Clin Cancer Res. 2016;22(21):5229–37. https://doi.org/10.1158/1078-0432.Ccr-15-2971.

    Article  CAS  Google Scholar 

  21. Cohen EE, Rosen F, Stadler WM, Recant W, Stenson K, et al. Phase II trial of ZD1839 in recurrent or metastatic squamous cell carcinoma of the head and neck. J Clin Oncol. 2003;21(10):1980–7. https://doi.org/10.1200/jco.2003.10.051.

    Article  CAS  Google Scholar 

  22. Erjala K, Sundvall M, Junttila TT, Zhang N, Savisalo M, et al. Signaling via ErbB2 and ErbB3 associates with resistance and epidermal growth factor receptor (EGFR) amplification with sensitivity to EGFR inhibitor gefitinib in head and neck squamous cell carcinoma cells. Clin Cancer Res. 2006;12(13):4103–11. https://doi.org/10.1158/1078-0432.Ccr-05-2404.

    Article  CAS  Google Scholar 

  23. Specenier P, Vermorken J. Afatinib in squamous cell carcinoma of the head and neck. Expert Opin Pharmacother. 2016;17(9):1295–301. https://doi.org/10.1080/14656566.2016.1183647.

    Article  CAS  Google Scholar 

  24. De Pauw I, Lardon F, Van den Bossche J, Baysal H, Fransen E, et al. Simultaneous targeting of EGFR, HER2, and HER4 by afatinib overcomes intrinsic and acquired cetuximab resistance in head and neck squamous cell carcinoma cell lines. Mol Oncol. 2018;12(6):830–54. https://doi.org/10.1002/1878-0261.12197.

    Article  CAS  Google Scholar 

  25. Zhang X, Shi M, Chen T, Zhang B. Characterization of the immune cell infiltration landscape in head and neck squamous cell carcinoma to aid immunotherapy. Mol Ther Nucleic Acids. 2020;22:298–309. https://doi.org/10.1016/j.omtn.2020.08.030.

    Article  CAS  Google Scholar 

  26. Kondo N, Tsukuda M, Taguchi T, Nakazaki K, Sakakibara A, et al. Gene status of head and neck squamous cell carcinoma cell lines and cetuximab-mediated biological activities. Cancer Sci. 2011;102(9):1717–23. https://doi.org/10.1111/j.1349-7006.2011.01999.x.

    Article  CAS  Google Scholar 

  27. Taylor RJ, Chan SL, Wood A, Voskens CJ, Wolf JS, et al. FcgammaRIIIa polymorphisms and cetuximab induced cytotoxicity in squamous cell carcinoma of the head and neck. Cancer Immunol Immunother. 2009;58(7):997–1006. https://doi.org/10.1007/s00262-008-0613-3.

    Article  CAS  Google Scholar 

  28. Lattanzio L, Denaro N, Vivenza D, Varamo C, Strola G, et al. Elevated basal antibody-dependent cell-mediated cytotoxicity (ADCC) and high epidermal growth factor receptor (EGFR) expression predict favourable outcome in patients with locally advanced head and neck cancer treated with cetuximab and radiotherapy. Cancer Immunol Immunother. 2017;66(5):573–9. https://doi.org/10.1007/s00262-017-1960-8.

    Article  CAS  Google Scholar 

  29. Yang X, Zhang X, Mortenson ED, Radkevich-Brown O, Wang Y, et al. Cetuximab-mediated tumor regression depends on innate and adaptive immune responses. Mol Ther. 2013;21(1):91–100. https://doi.org/10.1038/mt.2012.184.

    Article  CAS  Google Scholar 

  30. Fang J, Li X, Ma D, Liu X, Chen Y, et al. Prognostic significance of tumor infiltrating immune cells in oral squamous cell carcinoma. BMC Cancer. 2017;17(1):375. https://doi.org/10.1186/s12885-017-3317-2.

    Article  CAS  Google Scholar 

  31. Wagner S, Wittekindt C, Reuschenbach M, Hennig B, Thevarajah M, et al. CD56-positive lymphocyte infiltration in relation to human papillomavirus association and prognostic significance in oropharyngeal squamous cell carcinoma. Int J Cancer. 2016;138(9):2263–73. https://doi.org/10.1002/ijc.29962.

    Article  CAS  Google Scholar 

  32. Maréchal R, De Schutter J, Nagy N, Demetter P, Lemmers A, et al. Putative contribution of CD56 positive cells in cetuximab treatment efficacy in first-line metastatic colorectal cancer patients. BMC Cancer. 2010;10:340. https://doi.org/10.1186/1471-2407-10-340.

    Article  CAS  Google Scholar 

  33. Ferris RL, Saba NF, Gitlitz BJ, Haddad R, Sukari A, et al. Effect of adding motolimod to standard combination chemotherapy and cetuximab treatment of patients with squamous cell carcinoma of the head and neck: the Active8 randomized clinical trial. JAMA Oncol. 2018;4(11):1583–8. https://doi.org/10.1001/jamaoncol.2018.1888.

    Article  Google Scholar 

  34. Shayan G, Kansy BA, Gibson SP, Srivastava RM, Bryan JK, et al. Phase Ib study of immune biomarker modulation with neoadjuvant cetuximab and TLR8 stimulation in head and neck cancer to overcome suppressive myeloid signals. Clin Cancer Res. 2018;24(1):62–72. https://doi.org/10.1158/1078-0432.Ccr-17-0357.

    Article  CAS  Google Scholar 

  35. Chow LQM, Morishima C, Eaton KD, Baik CS, Goulart BH, et al. Phase Ib trial of the Toll-like receptor 8 agonist, motolimod (VTX-2337), combined with cetuximab in patients with recurrent or metastatic SCCHN. Clin Cancer Res. 2017;23(10):2442–50. https://doi.org/10.1158/1078-0432.Ccr-16-1934.

    Article  CAS  Google Scholar 

  36. Stephenson RM, Lim CM, Matthews M, Dietsch G, Hershberg R, et al. TLR8 stimulation enhances cetuximab-mediated natural killer cell lysis of head and neck cancer cells and dendritic cell cross-priming of EGFR-specific CD8+ T cells. Cancer Immunol Immunother. 2013;62(8):1347–57. https://doi.org/10.1007/s00262-013-1437-3.

    Article  CAS  Google Scholar 

  37. Kubach J, Hubo M, Amendt C, Stroh C, Jonuleit H. IgG1 anti-epidermal growth factor receptor antibodies induce CD8-dependent antitumor activity. Int J Cancer. 2015;136(4):821–30. https://doi.org/10.1002/ijc.29037.

    Article  CAS  Google Scholar 

  38. Gerdes CA, Nicolini VG, Herter S, van Puijenbroek E, Lang S, et al. GA201 (RG7160): a novel, humanized, glycoengineered anti-EGFR antibody with enhanced ADCC and superior in vivo efficacy compared with cetuximab. Clin Cancer Res. 2013;19(5):1126–38. https://doi.org/10.1158/1078-0432.Ccr-12-0989.

    Article  CAS  Google Scholar 

  39. Temam S, Spicer J, Farzaneh F, Soria JC, Oppenheim D, et al. An exploratory, open-label, randomized, multicenter study to investigate the pharmacodynamics of a glycoengineered antibody (imgatuzumab) and cetuximab in patients with operable head and neck squamous cell carcinoma. Ann Oncol. 2017;28(11):2827–35. https://doi.org/10.1093/annonc/mdx489.

    Article  CAS  Google Scholar 

  40. Pinette A, McMichael E, Courtney NB, Duggan M, Benner BN, et al. An IL-15-based superagonist ALT-803 enhances the NK cell response to cetuximab-treated squamous cell carcinoma of the head and neck. Cancer Immunol Immunother. 2019;68(8):1379–89. https://doi.org/10.1007/s00262-019-02372-2.

    Article  CAS  Google Scholar 

  41. Luedke E, Jaime-Ramirez AC, Bhave N, Roda J, Choudhary MM, et al. Cetuximab therapy in head and neck cancer: immune modulation with interleukin-12 and other natural killer cell-activating cytokines. Surgery. 2012;152(3):431–40. https://doi.org/10.1016/j.surg.2012.05.035.

    Article  Google Scholar 

  42. Jin WJ, Erbe AK, Schwarz CN, Jaquish AA, Anderson BR, et al. Tumor-specific antibody, cetuximab, enhances the in situ vaccine effect of radiation in immunologically cold head and neck squamous cell carcinoma. Front Immunol. 2020;11:591139. https://doi.org/10.3389/fimmu.2020.591139.

    Article  CAS  Google Scholar 

  43. Maleki Vareki S. High and low mutational burden tumors versus immunologically hot and cold tumors and response to immune checkpoint inhibitors. J Immunother Cancer. 2018;6(1):157. https://doi.org/10.1186/s40425-018-0479-7.

    Article  Google Scholar 

  44. Weil S, Memmer S, Lechner A, Huppert V, Giannattasio A, et al. Natural killer group 2D ligand depletion reconstitutes natural killer cell immunosurveillance of head and neck squamous cell carcinoma. Front Immunol. 2017;8:387. https://doi.org/10.3389/fimmu.2017.00387.

    Article  CAS  Google Scholar 

  45. Klöß S, Chambron N, Gardlowski T, Arseniev L, Koch J, et al. Increased sMICA and TGFβ(1) levels in HNSCC patients impair NKG2D-dependent functionality of activated NK cells. Oncoimmunology. 2015;4(11):e1055993. https://doi.org/10.1080/2162402x.2015.1055993.

    Article  Google Scholar 

  46. Vantourout P, Willcox C, Turner A, Swanson CM, Haque Y, et al. Immunological visibility: posttranscriptional regulation of human NKG2D ligandZs by the EGF receptor pathway. Sci Transl Med. 2014;6(231):231ra49. https://doi.org/10.1126/scitranslmed.3007579.

    Article  CAS  Google Scholar 

  47. Klöss S, Chambron N, Gardlowski T, Weil S, Koch J, et al. Cetuximab reconstitutes pro-inflammatory cytokine secretions and tumor-infiltrating capabilities of sMICA-inhibited NK cells in HNSCC tumor spheroids. Front Immunol. 2015;6:543. https://doi.org/10.3389/fimmu.2015.00543.

    Article  CAS  Google Scholar 

  48. Lu S, Concha-Benavente F, Shayan G, Srivastava RM, Gibson SP, et al. STING activation enhances cetuximab-mediated NK cell activation and DC maturation and correlates with HPV(+) status in head and neck cancer. Oral Oncol. 2018;78:186–93. https://doi.org/10.1016/j.oraloncology.2018.01.019.

    Article  CAS  Google Scholar 

  49. •• Hayman TJ, Baro M, MacNeil T, Phoomak C, Aung TN, et al. STING enhances cell death through regulation of reactive oxygen species and DNA damage. Nat Commun. 2021; 12(1); 2327.https://doi.org/10.1038/s41467-021-22572-8. It identifies STING as a critical determinant of ROS homeostasis to alter tumor survival and make it a principal strategy to improve the survival of HNSCC patients.

  50. Bauman JE, Ferris RL. Integrating novel therapeutic monoclonal antibodies into the management of head and neck cancer. Cancer. 2014;120(5):624–32. https://doi.org/10.1002/cncr.28380.

    Article  CAS  Google Scholar 

  51. Ferris RL, Whiteside TL, Ferrone S. Immune escape associated with functional defects in antigen-processing machinery in head and neck cancer. Clin Cancer Res. 2006;12(13):3890–5. https://doi.org/10.1158/1078-0432.Ccr-05-2750.

    Article  CAS  Google Scholar 

  52. Srivastava RM, Trivedi S, Concha-Benavente F, Hyun-Bae J, Wang L, et al. STAT1-induced HLA class I upregulation enhances immunogenicity and clinical response to anti-EGFR mAb cetuximab therapy in HNC patients. Cancer Immunol Res. 2015;3(8):936–45. https://doi.org/10.1158/2326-6066.Cir-15-0053.

    Article  CAS  Google Scholar 

  53. Leibowitz MS, Srivastava RM, Andrade Filho PA, Egloff AM, Wang L, et al. SHP2 is overexpressed and inhibits pSTAT1-mediated APM component expression, T-cell attracting chemokine secretion, and CTL recognition in head and neck cancer cells. Clin Cancer Res. 2013;19(4):798–808. https://doi.org/10.1158/1078-0432.Ccr-12-1517.

    Article  CAS  Google Scholar 

  54. Garrido G, Lorenzano P, Sánchez B, Beausoleil I, Alonso DF, et al. T cells are crucial for the anti-metastatic effect of anti-epidermal growth factor receptor antibodies. Cancer Immunol Immunother. 2007;56(11):1701–10. https://doi.org/10.1007/s00262-007-0313-4.

    Article  CAS  Google Scholar 

  55. Yao Z, Fenoglio S, Gao DC, Camiolo M, Stiles B, et al. TGF-beta IL-6 axis mediates selective and adaptive mechanisms of resistance to molecular targeted therapy in lung cancer. Proc Natl Acad Sci U S A. 2010;107(35):15535–40. https://doi.org/10.1073/pnas.1009472107.

    Article  Google Scholar 

  56. Xu Y, Gao Z, Hu R, Wang Y, Wang Y, et al. PD-L2 glycosylation promotes immune evasion and predicts anti-EGFR efficacy. J Immunother Cancer. 2021;9(10):e002699. https://doi.org/10.1136/jitc-2021-002699

  57. Jie HB, Srivastava RM, Argiris A, Bauman JE, Kane LP, et al. Increased PD-1(+) and TIM-3(+) TILs during cetuximab therapy inversely correlate with response in head and neck cancer patients. Cancer Immunol Res. 2017;5(5):408–16. https://doi.org/10.1158/2326-6066.Cir-16-0333.

    Article  CAS  Google Scholar 

  58. Wang Z, Goto Y, Allevato MM, Wu VH, Saddawi-Konefka R, et al. Disruption of the HER3-PI3K-mTOR oncogenic signaling axis and PD-1 blockade as a multimodal precision immunotherapy in head and neck cancer. Nat Commun. 2021;12(1):2383. https://doi.org/10.1038/s41467-021-22619-w.

  59. Cheng CC, Lin HC, Tsai KJ, Chiang YW, Lim KH, et al. Epidermal growth factor induces STAT1 expression to exacerbate the IFNr-mediated PD-L1 axis in epidermal growth factor receptor-positive cancers. Mol Carcinog. 2018;57(11):1588–98. https://doi.org/10.1002/mc.22881.

    Article  CAS  Google Scholar 

  60. •• Lee JC, Wu ATH, Chen JH, Huang WY, Lawal B, et al. HNC0014, a multi-targeted small-molecule, inhibits head and neck squamous cell carcinoma by suppressing c-Met/STAT3/CD44/PD-L1 oncoimmune signature and eliciting antitumor immune responses. Cancers (Basel). 2020; 12(12).https://doi.org/10.3390/cancers12123759. Demonstrates a small molecule drug, HNC0014, suppresses the development of HNSCC by downregulating c-Met/STAT/CD44/PD-L1 and the phosphorylated c-Met/STAT signature.

  61. Feng B, Shen Y, Pastor Hostench X, Bieg M, Plath M, et al. Integrative analysis of multi-omics data identified EGFR and PTGS2 as key nodes in a gene regulatory network related to immune phenotypes in head and neck cancer. Clin Cancer Res. 2020;26(14):3616–28. https://doi.org/10.1158/1078-0432.Ccr-19-3997.

    Article  CAS  Google Scholar 

  62. Gribben JG, Fowler N, Morschhauser F. Mechanisms of action of lenalidomide in B-cell non-Hodgkin lymphoma. J Clin Oncol. 2015;33(25):2803–11. https://doi.org/10.1200/jco.2014.59.5363.

    Article  CAS  Google Scholar 

  63. Bertino EM, McMichael EL, Mo X, Trikha P, Davis M, et al. A phase I trial to evaluate antibody-dependent cellular cytotoxicity of cetuximab and lenalidomide in advanced colorectal and head and neck cancer. Mol Cancer Ther. 2016;15(9):2244–50. https://doi.org/10.1158/1535-7163.Mct-15-0879.

    Article  CAS  Google Scholar 

  64. Ruzsa A, Sen M, Evans M, Lee LW, Hideghety K, et al. Phase 2, open-label, 1:1 randomized controlled trial exploring the efficacy of EMD 1201081 in combination with cetuximab in second-line cetuximab-naïve patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). Invest New Drugs. 2014;32(6):1278–84. https://doi.org/10.1007/s10637-014-0117-2.

    Article  CAS  Google Scholar 

  65. Srivastava RM, Trivedi S, Concha-Benavente F, Gibson SP, Reeder C, et al. CD137 stimulation enhances cetuximab-induced natural killer: dendritic cell priming of antitumor T-cell immunity in patients with head and neck cancer. Clin Cancer Res. 2017;23(3):707–16. https://doi.org/10.1158/1078-0432.Ccr-16-0879.

    Article  CAS  Google Scholar 

  66. Topalian SL, Taube JM, Pardoll DM. Neoadjuvant checkpoint blockade for cancer immunotherapy. Science. 2020;367(6477):eaax0182. https://doi.org/10.1126/science.aax0182

  67. Kansy BA, Shayan G, Jie HB, Gibson SP, Lei YL, et al. T cell receptor richness in peripheral blood increases after cetuximab therapy and correlates with therapeutic response. Oncoimmunology. 2018;7(11):e1494112. https://doi.org/10.1080/2162402x.2018.1494112.

    Article  CAS  Google Scholar 

  68. Tian Y, Zhang L, Jin N, Wan Z, Zhang H, et al. Clinical response to neoadjuvant immunotherapy combined with targeted therapy and chemotherapy in oral squamous cell carcinoma: experience in three patients. Onco Targets Ther. 2022;15:353–9. https://doi.org/10.2147/ott.S355349.

    Article  CAS  Google Scholar 

  69. Leblanc O, Vacher S, Lecerf C, Jeannot E, Klijanienko J, et al. Biomarkers of cetuximab resistance in patients with head and neck squamous cell carcinoma. Cancer Biol Med. 2020;17(1):208–17. https://doi.org/10.20892/j.issn.2095-3941.2019.0153.

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by the China National Natural Scientific Fund Nos. 81872206 (to X.Z.), 82073010 (to X.Z.), 81872495 (to Y.R.), 82172764 (to Y.R.), and 82002892(to Y.W.) and the Tianjin Education Commission Funded Projects No. 2019KJ188 (to Y.W.).

The tables and figures included in this paper are original.

Author information

Author notes

  1. Lin Dong and Yu Wang contributed equally.

Authors and Affiliations

  1. Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China

    Lin Dong, Yu Wang, Xiaofeng Yao & Xuan Zhou

  2. Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute, Tianjin, 300060, China

    Lin Dong, Yu Wang, Xiaofeng Yao & Xuan Zhou

  3. National Clinical Research Center of Cancer, Tianjin, 300060, China

    Lin Dong, Yu Wang, Xiaofeng Yao & Xuan Zhou

  4. Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China

    Yu Ren

Authors
  1. Lin Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaofeng Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yu Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xuan Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Xuan Zhou had the idea for the article. Lin Dong performed the literature research and drafted the work. Yu Wang, Yu Ren, and Xiaofeng Yao critically revised the work.

Corresponding authors

Correspondence to Yu Ren or Xuan Zhou.

Ethics declarations

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Head and Neck Cancers

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dong, L., Wang, Y., Yao, X. et al. Novel Insights of Anti-EGFR Therapy in HNSCC: Combined with Immunotherapy or Not?. Curr Oncol Rep 25, 93–105 (2023). https://doi.org/10.1007/s11912-022-01349-2

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11912-022-01349-2

Keywords

Search

Navigation