帕博利珠单抗联合二甲双胍治疗转移性头颈部癌的 II 期可行性研究
A Phase II Feasibility Study Combining Pembrolizumab and Metformin in Patients with Metastatic Head and Neck Cancer.
二甲双胍联合帕博利珠单抗耐受性良好,仅出现轻度胃肠道不良事件,并展现出有前景的活性,值得在随机试验中进一步研究。
英文原题:Unraveling the Role of Tumor-Infiltrating Immune Cells in Head and Neck Squamous Cell Carcinoma: Implications for Antitumor Immune Responses and Immunotherapy.
头颈部鳞状细胞癌(HNSCC)是一种高度异质性的恶性肿瘤,其特征是复杂的肿瘤微环境(TME),在疾病进展和治疗耐药中起关键作用。
头颈部鳞状细胞癌(HNSCC)是一种高度异质性的恶性肿瘤,其特征是复杂的肿瘤微环境(TME),在疾病进展和治疗耐药中起关键作用。肿瘤浸润免疫细胞,包括T淋巴细胞、巨噬细胞、树突状细胞和髓源性抑制细胞,表现出双重功能,根据其表型及在TME中的相互作用,或促进或抑制肿瘤生长。免疫逃逸机制的存在,如人类白细胞抗原(HLA)表达缺失、免疫检查点分子上调以及代谢重编程(缺氧诱导的糖酵解和乳酸积累),进一步导致免疫抑制和治疗反应不佳。尽管免疫检查点抑制剂(ICIs)已彻底改变了复发/转移性HNSCC的治疗,但应答率仍高度可变,凸显了基于生物标志物的患者筛选和联合治疗策略的必要性。本综述全面分析了免疫细胞在HNSCC的TME中的作用,讨论了免疫逃逸的机制,并探讨了旨在增强抗肿瘤免疫应答和改善临床结局的新兴免疫治疗和表观遗传靶向方法。
Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous malignancy characterized by a complex tumor microenvironment (TME) that plays a critical role in disease progression and therapeutic resistance. Tumor-infiltrating immune cells, including T lymphocytes, macrophages, dendritic cells, and myeloid-derived suppressor cells, exhibit dual functions, either promoting or suppressing tumor growth depending on their phenotype and interactions within the TME. The presence of immune evasion mechanisms, such as the loss of human leukocyte antigen ( HLA ) expression, upregulation of immune checkpoint molecules, and metabolic reprogramming (hypoxia-induced glycolysis and lactate accumulation), further contributes to immune suppression and poor treatment responses. While immune checkpoint inhibitors (ICIs) have revolutionized the treatment of recurrent/metastatic HNSCC, response rates remain highly variable, underscoring the need for biomarker-driven patient selection and combinatorial therapeutic strategies. This review provides a comprehensive analysis of the role of immune cells in the TME of HNSCC, discusses the mechanisms underlying immune escape, and explores emerging immunotherapeutic and epigenetic-targeting approaches aimed at enhancing antitumor immune responses and improving clinical outcomes.
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