Improving head and neck cancer therapies by immunomodulation of the tumour microenvironment

Nat Rev Cancer. 2023 Mar;23(3):173-188. doi: 10.1038/s41568-022-00531-9. Epub 2022 Dec 1.


Targeted immunotherapy has improved patient survival in head and neck squamous cell carcinoma (HNSCC), but less than 20% of patients produce a durable response to these treatments. Thus, new immunotherapies that consider all key players of the complex HNSCC tumour microenvironment (TME) are necessary to further enhance tumour-specific T cell responses in patients. HNSCC is an ideal tumour type in which to evaluate immune and non-immune cell differences because of two distinct TME aetiologies (human papillomavirus (HPV)-positive and HPV-negative disease), multiple anatomic sites for tumour growth, and clear distinctions between patients with locally advanced disease and those with recurrent and/or metastatic disease. Recent technological and scientific advancements have provided a more complete picture of all cellular constituents within this complex TME and have evaluated the interplay of both immune and non-immune cells within HNSCC. Here, we include a comprehensive analysis of the complete ecosystem of the HNSCC TME, performed utilizing data-rich resources such as The Cancer Genome Atlas, and cutting-edge techniques, such as single-cell RNA sequencing, high-dimensional flow cytometry and spatial multispectral imaging, to generate improved treatment strategies for this diverse disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Antineoplastic Agents, Immunological* / immunology
  • Antineoplastic Agents, Immunological* / therapeutic use
  • Head and Neck Neoplasms* / etiology
  • Head and Neck Neoplasms* / immunology
  • Head and Neck Neoplasms* / therapy
  • Humans
  • Immunomodulation*
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / immunology
  • Squamous Cell Carcinoma of Head and Neck* / etiology
  • Squamous Cell Carcinoma of Head and Neck* / immunology
  • Squamous Cell Carcinoma of Head and Neck* / therapy
  • Tumor Microenvironment* / immunology


  • Antineoplastic Agents, Immunological