定向免疫治疗已经改善了头颈部鳞状细胞癌（HNSCC）患者的生存率，但少于20%的患者对这些治疗能够产生持久的反应。因此，需要新的免疫疗法来考虑复杂的HNSCC肿瘤微环境（TME）中的所有关键因素，以进一步增强患者的肿瘤特异性T细胞反应。HNSCC是一种理想的肿瘤类型，可用于评估免疫和非免疫细胞之间的差异，因为它有两种截然不同的TME病因（人类乳头瘤病毒（HPV）阳性和HPV阴性疾病），多种解剖学部位的肿瘤生长，并且患者之间有明显的区别，有局部晚期疾病和有复发和/或转移疾病的患者。最近的技术和科学进步提供了更完整的所有细胞组成的图像，评估了HNSCC内免疫和非免疫细胞之间的相互作用。在这里，我们包括了对HNSCC TME完整生态系统的全面分析，利用如癌症基因组图谱等数据丰富的资源，以及单细胞RNA测序，高维流式细胞术和空间多光谱成像等尖端技术，为这种多样化的疾病生成改进的治疗策略。© 2022. Springer Nature Limited.

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.© 2022. Springer Nature Limited.