SpringerLink
Log in

Research progress of immunotherapy for advanced head and neck cancer

  • Review Article
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Head and neck cancer accounts for about one-fifth of all malignant tumors, and the incidence is increasing year by year. The overall mortality rate was high and the 5-year survival rate was low. At present, the combination of surgery, radiotherapy, and chemotherapy is the main treatment in clinical practice, but the treatment of recurrent or metastatic advanced head and neck cancer is still a challenge. With the rise of immunotherapy, more and more studies on immune checkpoint inhibitors have been conducted. This review summarizes the mechanism, clinical application and safety of immunotherapy for advanced head and neck cancer.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Data availability

Not applicable.

Abbreviations

HNSCC:

Head and neck cancer

TAAs:

Tumor-associated antigens

APCs:

Antigen-presenting cells

NK:

Natural killer

TME:

Tumor microenvironment

MHC:

Major histocompatibility complex

ICIs:

Immune checkpoint inhibitors

PD-1:

Programmed death receptor 1

PD-L1:

Programmed death ligand 1

CTLA-4:

Cytotoxic T lymphocyte-associated protein 4

R/M HNSCC:

Recurrent and metastatic head and neck squamous cell carcinoma

PFS:

Progression-free survival

OS:

Overall survival

DOR:

Duration of response

ORR:

Objective response rate

CSCO:

Chinese Society of Clinical Oncology

PPS:

Post-progression survival

HPV:

Human papillomavirus

AEs:

Adverse events

CPS:

Combined positive score

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7–34.

    Article  PubMed  Google Scholar 

  2. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.

    Article  PubMed  Google Scholar 

  3. Zheng R, Zhang S, Zeng H, et al. Cancer incidence and mortality in China, 2016. J Natl Cancer Center. 2022;2(1):1–9.

    Article  Google Scholar 

  4. Cramer JD, Burtness B, Le QT, et al. The changing therapeutic landscape of head and neck cancer. Nat Rev Clin Oncol. 2019;16(11):669–83.

    Article  PubMed  Google Scholar 

  5. Larkins E, Blumenthal GM, Yuan W, et al. FDA approval summary: pembrolizumab for the treatment of recurrent or metastatic head and neck squamous cell carcinoma with disease progression on or after platinum-containing chemotherapy. Oncologist. 2017;22(7):873–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Nwizu T, Adelstein D. Pharmacotherapy of head and neck cancer. Expert Opin Pharmacother. 2015;16(16):2409–22.

    Article  CAS  PubMed  Google Scholar 

  7. Seiwert TY, Cohen EE. State-of-the-art management of locally advanced head and neck cancer. Br J Cancer. 2005;92(8):1341–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Coley WBII. Contribution to the knowledge of sarcoma. Ann Surg. 1891;14(3):199–220.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Dunn GP, Bruce AT, Ikeda H, et al. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002;3(11):991–8.

    Article  CAS  PubMed  Google Scholar 

  10. Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol. 2004;22:329–60.

    Article  CAS  PubMed  Google Scholar 

  11. O’Donnell JS, Teng MWL, Smyth MJ. Cancer immunoediting and resistance to T cell-based immunotherapy. Nat Rev Clin Oncol. 2019;16(3):151–67.

    Article  PubMed  Google Scholar 

  12. Sivori S, Pende D, Quatrini L, et al. NK cells and ILCs in tumor immunotherapy. Mol Aspects Med. 2021;80:100870.

    Article  CAS  PubMed  Google Scholar 

  13. Chen Y, Guan M, Ren R, et al. Improved immunoregulation of ultra-low-dose silver nanoparticle-loaded TiO(2) nanotubes via M2 macrophage polarization by regulating GLUT1 and autophagy. Int J Nanomed. 2020;15:2011–26.

    Article  CAS  Google Scholar 

  14. Daar AS, Fuggle SV, Fabre JW, et al. The detailed distribution of MHC Class II antigens in normal human organs. Transplantation. 1984;38(3):293–8.

    Article  CAS  PubMed  Google Scholar 

  15. Coulie PG, Van Den Eynde BJ, Van Der Bruggen P, et al. Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy. Nat Rev Cancer. 2014;14(2):135–46.

    Article  CAS  PubMed  Google Scholar 

  16. Sahin U, Derhovanessian E, Miller M, et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature. 2017;547(7662):222–6.

    Article  CAS  PubMed  Google Scholar 

  17. Toor SM, Sasidharan Nair V, Decock J, et al. Immune checkpoints in the tumor microenvironment. Semin Cancer Biol. 2020;65:1–12.

    Article  CAS  PubMed  Google Scholar 

  18. Grimmig T, Gasser M, Moench R, et al. Expression of tumor-mediated CD137 ligand in human colon cancer indicates dual signaling effects. Oncoimmunology. 2019;8(12):e1651622.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Etxeberria I, Glez-Vaz J, Teijeira A, et al. New emerging targets in cancer immunotherapy: CD137/4-1BB costimulatory axis. ESMO Open. 2020;4(Suppl 3):e000733.

    PubMed  PubMed Central  Google Scholar 

  20. Vonderheide RH. CD40 agonist antibodies in cancer immunotherapy. Annu Rev Med. 2020;71:47–58.

    Article  CAS  PubMed  Google Scholar 

  21. Payne KK, Mine JA, Biswas S, et al. BTN3A1 governs antitumor responses by coordinating alphabeta and gammadelta T cells. Science. 2020;369(6506):942–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Sunshine J, Taube JM. PD-1/PD-L1 inhibitors. Curr Opin Pharmacol. 2015;23:32–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Francisco LM, Sage PT, Sharpe AH. The PD-1 pathway in tolerance and autoimmunity. Immunol Rev. 2010;236:219–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Boussiotis VA, Chatterjee P, Li L. Biochemical signaling of PD-1 on T cells and its functional implications. Cancer J. 2014;20(4):265–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Krummel MF, Allison JP. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J Exp Med. 1995;182(2):459–65.

    Article  CAS  PubMed  Google Scholar 

  26. Sobhani N, Tardiel-Cyril DR, Davtyan A, et al. CTLA-4 in regulatory T cells for cancer immunotherapy. Cancers (Basel). 2021;13(6):1440.

    Article  CAS  PubMed  Google Scholar 

  27. Pentcheva-Hoang T, Egen JG, Wojnoonski K, et al. B7-1 and B7-2 selectively recruit CTLA-4 and CD28 to the immunological synapse. Immunity. 2004;21(3):401–13.

    Article  CAS  PubMed  Google Scholar 

  28. Lan X, Yang TTC, Wang Y, et al. Characterization of 405B8H3(D-E), a newly engineered high affinity chimeric LAG-3 antibody with potent antitumor activity. FEBS Open Bio. 2023;13(7):1253–1265.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Wang J, Sanmamed MF, Datar I, et al. Fibrinogen-like protein 1 is a major immune inhibitory ligand of LAG-3. Cell. 2019;176(1–2):334–47 e12.

    Article  CAS  PubMed  Google Scholar 

  30. Wolf Y, Anderson AC, Kuchroo VK. TIM3 comes of age as an inhibitory receptor. Nat Rev Immunol. 2020;20(3):173–85.

    Article  CAS  PubMed  Google Scholar 

  31. Cazzetta V, Depierreux D, Colucci F, et al. NKG2A immune checkpoint in Vdelta2 T cells: emerging application in cancer immunotherapy. Cancers (Basel). 2023;15(4):1264.

    Article  CAS  PubMed  Google Scholar 

  32. Chow LQM, Haddad R, Gupta S, et al. 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. 2016;34(32):3838–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Cohen EEW, Soulieres D, Le Tourneau C, et al. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. The Lancet. 2019;393(10167):156–67.

    Article  CAS  Google Scholar 

  34. Burtness B, Harrington KJ, Greil R, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. The Lancet. 2019;394(10212):1915–28.

    Article  CAS  Google Scholar 

  35. Harrington KJ, Burtness B, Greil R, et al. Pembrolizumab with or without chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma: updated results of the phase III KEYNOTE-048 study. J Clin Oncol. 2023;41(4):790–802.

    Article  CAS  PubMed  Google Scholar 

  36. Yen CJ, Kiyota N, Hanai N, et al. Two-year follow-up of a randomized phase III clinical trial of nivolumab vs. the investigator’s choice of therapy in the Asian population for recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141). Head Neck. 2020;42(10):2852–62.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Saba NF, Blumenschein G Jr, Guigay J, et al. 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. 2019;96:7–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Zandberg DP, Algazi AP, Jimeno A, et al. 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. 2019;107:142–52.

    Article  CAS  PubMed  Google Scholar 

  39. Siu LL, Even C, Mesia R, et al. Safety and efficacy of durvalumab with or without tremelimumab in patients with PD-L1-low/negative recurrent or metastatic HNSCC: the phase 2 CONDOR randomized clinical trial. JAMA Oncol. 2019;5(2):195–203.

    Article  PubMed  Google Scholar 

  40. Kim H, Park S, Jung HA, et al. Phase II trial of combined durvalumab plus tremelimumab with proton therapy for recurrent or metastatic head and neck squamous cell carcinoma. Cancer Res Treat. 2023;55(4):1104–1112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Haddad RI, Harrington K, Tahara M, et al. Nivolumab plus ipilimumab versus EXTREME regimen as first-line treatment for recurrent/metastatic squamous cell carcinoma of the head and neck: the final results of CheckMate 651. J Clin Oncol. 2023;41(12):2166–80.

    Article  CAS  PubMed  Google Scholar 

  42. Harrington KJ, Ferris RL, Gillison M, et al. Efficacy and safety of nivolumab plus ipilimumab vs nivolumab alone for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck: the phase 2 CheckMate 714 randomized clinical trial. JAMA Oncol. 2023;9(6):779–89.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Segal NH, Ou SI, Balmanoukian A, et al. Safety and efficacy of durvalumab in patients with head and neck squamous cell carcinoma: results from a phase I/II expansion cohort. Eur J Cancer. 2019;109:154–61.

    Article  CAS  PubMed  Google Scholar 

  44. Ferris RL, Moskovitz J, Kunning S, et al. Phase I trial of cetuximab, radiotherapy, and ipilimumab in locally advanced head and neck cancer. Clin Cancer Res. 2022;28(7):1335–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Cesaire M, Rambeau A, Clatot F, et al. Impact of lymphopenia on efficacy of nivolumab in head and neck cancer patients. Eur Arch Otorhinolaryngol. 2023;280(5):2453–61.

    Article  PubMed  Google Scholar 

Download references

Funding

This work was supported by partly grants from the National Natural Science Foundation of China (81903142 and 82372786), the Anhui Province University Outstanding Youth Research Project (2023AH020049) and the First Affiliated Hospital of Bengbu Medical College Science Fund for Excellent Youth (2019byyfyyq03).

Author information

Authors and Affiliations

  1. Department of Otolaryngology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233004, Anhui, China

    Anchi Sun, Zhiwei **ng, Rongrong Lv, Bao Zhao, Shiyin Ma & Hui Li

  2. Anhui Engineering Technology Research Center of Biochemical Pharmaceutical, 2600 Donghai Avenue, Bengbu, 233030, Anhui, China

    Anchi Sun

  3. Department of Neurosurgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233004, Anhui, China

    Pengyuan Niu

  4. Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei, 230071, Anhui, China

    Bao Zhao

Authors
  1. Anchi Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhiwei **ng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rongrong Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pengyuan Niu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bao Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shiyin Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hui Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Anchi Sun, Pengyuan Niu, and Hui Li. The first draft of the manuscript was written by Anchi Sun. Zhiwei **ng and Rongrong Lv prepared Figs. 1, 2 and Table 1. Dr. Bao Zhao participated in the early revision and polishing of the manuscript, and provided financial assistance; Dr. Shiyin Ma commented on the errors in Figs. 1 and 2 and corrected them. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Shiyin Ma or Hui Li.

Ethics declarations

Competing interests

The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publish

Not applicable.

Additional information

Publisher's Note

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

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

Sun, A., **ng, Z., Lv, R. et al. Research progress of immunotherapy for advanced head and neck cancer. Med Oncol 41, 133 (2024). https://doi.org/10.1007/s12032-024-02375-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-024-02375-9

Keywords

Search

Navigation