Head and Neck Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Unit of Immunotherapy of Human Tumors, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Cancer Treat Rev. 2018 Apr;65:78-86. doi: 10.1016/j.ctrv.2018.03.003. Epub 2018 Mar 20.
According to the new determinants of cancer immunity, head and neck squamous cell cancer (HNSCC) has to be considered as an immunogenic tumor for the relatively high number of somatic mutations giving rise to neoantigens recognized by T cell. HNSCC develop at a significant rate despite the antitumoral immune response indicating the existence of effective escape mechanisms. The lack of antigen presentation or co-stimulatory molecules required and immunosuppressive phenomena established by the tumor or the host microenvironment impair immune-mediated recognition and cancer control. Echoing the success in melanoma and NSCLC, strategies aimed to reverse this process and enhance the antitumor immunity are rapidly developing in HNSCC, as monotherapies, multidrug immunotherapies or associations with well-recognized treatments, like radiation and systemic therapies. According to the first published data, immunotherapy has shown promising results in the management of recurrent and metastatic (r/m) HNSCC. Anti-PD-1 blockers have been recently approved by US and EU regulatory agencies in this setting. The encouraging results in r/m HNSCC prompted the incorporation of this approach also in the treatment of locally advanced disease. However, the strategies for the rational and evidence-based combinations to maximize clinical benefit are only starting to emerge. In this view, knowing in depth the specific properties of HNSCC and the underlying immunological conditions of the bearing hosts is an essential step. The role of immune system in the development and the management of HNSCC, the main mechanisms of tumor escape and the most recent results from clinical trials will be discussed herein.
根据癌症免疫的新决定因素，头颈部鳞状细胞癌（HNSCC）必须被视为一种免疫原性肿瘤，因为其相对较高数量的体细胞突变产生了被 T 细胞识别的新抗原。尽管存在抗肿瘤免疫反应，但 HNSCC 仍以相当高的速度发展，这表明存在有效的逃逸机制。肿瘤或宿主微环境中缺乏抗原呈递或共刺激分子，以及建立的免疫抑制现象，损害了免疫介导的识别和癌症控制。与黑色素瘤和 NSCLC 的成功相呼应，旨在逆转这一过程并增强抗肿瘤免疫的策略在 HNSCC 中迅速发展，作为单药治疗、多药免疫治疗或与公认的治疗方法（如放疗和全身治疗）联合应用。根据首次发表的数据，免疫疗法在复发性和转移性（r/m）HNSCC 的治疗中显示出有希望的结果。抗 PD-1 阻滞剂最近已被美国和欧盟监管机构批准用于该适应症。r/m HNSCC 的令人鼓舞的结果促使该方法也被纳入局部晚期疾病的治疗。然而，为了最大限度地提高临床获益而进行合理和基于证据的联合治疗的策略才刚刚开始出现。在这方面，深入了解 HNSCC 的特定性质和承载宿主的潜在免疫学条件是至关重要的一步。本文将讨论免疫系统在 HNSCC 的发展和管理中的作用、肿瘤逃逸的主要机制以及临床试验的最新结果。
