Immune-checkpoint inhibitors (ICIs) are being tested as neoadjuvant therapies in various solid tumours, including in patients with head and neck squamous cell carcinoma (HNSCC), with promising results. Key findings thus far include that this approach is well-tolerated with favourable clinical outcomes including promising pathological response rates in initial studies. Pathological responses are likely to be increased by combining other agents with anti-PD-(L)1 antibodies. Comparisons of baseline biopsy samples with post-treatment surgical specimens have enabled correlative studies utilizing multiomic and immunogenomic methods. Data from these studies suggest that pretreatment intratumoural tissue-resident memory CD8⁺ T cells are key drivers of tumour regression and give rise to both local and systemic antitumour immune responses. Analyses of systemic responses have defined a PD-1⁺KLRG1⁻ circulating CD8⁺ T cell subpopulation that is highly predictive of response, and revealed the interrelationships between intratumoural clones and circulating CD8⁺ T cells. Lastly, interrogation of T cell populations within lymph nodes is beginning to delineate the immune crosstalk between the primary tumour and tumour-draining lymph nodes and how this relationship might be disrupted with tumour infiltration of the latter. In this Review, we examine data from trials testing neoadjuvant ICIs in patients with HNSCC, focusing on human papillomavirus-unrelated disease, and highlight correlative immunogenomic findings from these trials.

免疫检查点抑制剂 （ICI） 正在各种实体瘤中作为新辅助疗法进行测试，包括头颈部鳞状细胞癌 （HNSCC） 患者，并取得了可喜的结果。迄今为止的主要发现包括这种方法耐受性良好，临床结果良好，包括初始研究中有希望的病理反应率。其他药物与抗 PD-（L）1 抗体联合使用可能会增加病理反应。基线活检样本与治疗后手术样本的比较使利用多组学和免疫基因组学方法的相关研究成为可能。这些研究的数据表明，治疗前肿瘤内组织驻留记忆 CD8⁺ T 细胞是肿瘤消退的关键驱动因素，并引起局部和全身抗肿瘤免疫反应。全身反应分析定义了 PD-1⁺KLRG1⁻ 循环 CD8⁺ T 细胞亚群，该亚群对反应具有高度预测性，并揭示了肿瘤内克隆与循环 CD8⁺ T 细胞之间的相互关系。最后，对淋巴结内 T 细胞群的询问开始描绘原发性肿瘤和肿瘤引流淋巴结之间的免疫串扰，以及后者的肿瘤浸润如何破坏这种关系。在本综述中，我们检查了在 HNSCC 患者中测试新辅助 ICIs 的试验数据，重点关注人瘤病毒无关疾病，并强调了这些试验的相关免疫基因组学发现。