Translational Cancer Research Facility, National Center for Cancer Care and Research/ Translational Research Institute, Hamad Medical Corporation, Doha, Qatar; National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar.
Translational Cancer Research Facility, National Center for Cancer Care and Research/ Translational Research Institute, Hamad Medical Corporation, Doha, Qatar; College of Medicine, Qatar University, Doha, Qatar.
Biomed Pharmacother. 2024 Feb;171:116095. doi: 10.1016/j.biopha.2023.116095. Epub 2024 Jan 6.
Head and neck cancer (HNC) is the sixth most common cancer type, accounting for approximately 277,597 deaths worldwide. Recently, the Food and Drug Administration (FDA) has approved immune checkpoint blockade (ICB) agents targeting programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) as a treatment regimen for head and neck squamous cell carcinomas (HNSCC). Studies have reported the role of immune checkpoint inhibitors as targeted therapeutic regimens that unleash the immune response against HNSCC tumors. However, the overall response rates to immunotherapy vary between 14-32% in recurrent or metastatic HNSCC, with clinical response and treatment success being unpredictable. Keeping this perspective in mind, it is imperative to understand the role of T cells, natural killer cells, and antigen-presenting cells in modulating the immune response to immunotherapy. In lieu of this, these immune molecules could serve as prognostic and predictive biomarkers to facilitate longitudinal monitoring and understanding of treatment dynamics. These immune biomarkers could pave the path for personalized monitoring and management of HNSCC. In this review, we aim to provide updated immunological insight on the mechanism of action, expression, and the clinical application of immune cells' stimulatory and inhibitory molecules as prognostic and predictive biomarkers in HNC. The review is focused mainly on CD27 and CD137 (members of the TNF-receptor superfamily), natural killer group 2 member D (NKG2D), tumor necrosis factor receptor superfamily member 4 (TNFRSF4 or OX40), S100 proteins, PD-1, PD-L1, PD-L2, T cell immunoglobulin and mucin domain 3 (TIM-3), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), lymphocyte-activation gene 3 (LAG-3), indoleamine-pyrrole 2,3-dioxygenase (IDO), B and T lymphocyte attenuator (BTLA). It also highlights the importance of T, natural killer, and antigen-presenting cells as robust biomarker tools for understanding immune checkpoint inhibitor-based treatment dynamics. Though a comprehensive review, all aspects of the immune molecules could not be covered as they were beyond the scope of the review; Further review articles can cover other aspects to bridge the knowledge gap.
头颈部癌症（HNC）是第六种最常见的癌症类型，占全球约 277597 例死亡。最近，美国食品和药物管理局（FDA）已批准针对程序性死亡受体-1（PD-1）和程序性死亡配体 1（PD-L1）的免疫检查点阻断（ICB）药物作为头颈部鳞状细胞癌（HNSCC）的治疗方案。研究报道了免疫检查点抑制剂作为靶向治疗方案的作用，这些方案释放了针对 HNSCC 肿瘤的免疫反应。然而，在复发性或转移性 HNSCC 中，免疫疗法的总体反应率在 14-32%之间，临床反应和治疗成功是不可预测的。考虑到这一点，了解 T 细胞、自然杀伤细胞和抗原呈递细胞在调节免疫反应中的作用至关重要。为此，这些免疫分子可以作为预后和预测生物标志物，以促进对治疗动态的纵向监测和理解。这些免疫生物标志物可以为 HNSCC 的个性化监测和管理铺平道路。在本综述中，我们旨在提供有关免疫细胞刺激和抑制分子作为 HNC 中预后和预测生物标志物的作用机制、表达和临床应用的最新免疫学见解。综述主要集中在 TNF 受体超家族成员 CD27 和 CD137、自然杀伤组 2 成员 D（NKG2D）、肿瘤坏死因子受体超家族成员 4（TNFRSF4 或 OX40）、S100 蛋白、PD-1、PD-L1、PD-L2、T 细胞免疫球蛋白和粘蛋白结构域 3（TIM-3）、细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）、淋巴细胞激活基因 3（LAG-3）、吲哚胺-2,3-双加氧酶（IDO）、B 和 T 淋巴细胞衰减器（BTLA）上。它还强调了 T、自然杀伤和抗原呈递细胞作为理解免疫检查点抑制剂治疗动态的强大生物标志物工具的重要性。尽管这是一项全面的综述，但由于超出了综述的范围，无法涵盖免疫分子的所有方面；进一步的综述文章可以涵盖其他方面来弥补知识空白。
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