肿瘤细胞治疗研究
英文原题：Precision immuno-oncology in oral cancer: latest trends in biomarkers, novel drug development and nanoparticle-based therapeutic platforms.
Precision immuno-oncology in oral cancer: latest trends in biomarkers, novel drug development and nanoparticle-based therapeutic platforms.
口腔鳞状细胞癌构成了重大的全球健康负担，每年新增病例超过370,000例，5年生存率仅为50%-60%，烟草和酒精等风险因素是其重要驱动因素。
口腔鳞状细胞癌构成了重大的全球健康负担，每年新增病例超过370,000例，5年生存率仅为50%-60%，烟草和酒精等风险因素是其驱动因素。尽管手术、放疗和化疗取得了进展，但功能性发病和耐药性使得精准免疫肿瘤学方法成为必要。本综述探讨了口腔鳞状细胞癌的肿瘤免疫微环境，其特征为M2巨噬细胞、髓源性抑制细胞和调节性T细胞等免疫抑制元素，以及使治疗复杂化的空间异质性。用于患者选择的生物标志物包括programmed death-ligand1表达（通过联合阳性评分）、肿瘤突变负荷、新抗原负荷、interferon-gamma-γ特征、细胞溶解评分、外周循环肿瘤DNA以及单细胞/空间分析，但标准化仍然至关重要。免疫治疗已改变了口腔鳞状细胞癌的管理，nivolumab和pembrolizumab等programmed cell death protein-1抑制剂在试验中显示出生存获益，尤其是在programmed cell death protein-L1阳性病例中。新兴策略包括下一代检查点（Lymphocyte activation gene-3、T-cell immunoreceptor with Ig and ITIM domains、OX40）、个性化新抗原疫苗、过继细胞疗法（Tumour-Infiltrating Lymphocytes、Chimeric Antigen Receptor T-cell therapy）以及合理的联合方案以对抗耐药性。纳米医学平台——脂质体、聚合物纳米颗粒、金基系统——增强药物递送，重编程肿瘤和免疫微环境，并实现化学-免疫-光热协同作用，解决黏膜屏障和毒性问题。未来优先事项包括通过前瞻性注册研究进行生物标志物验证、可扩展的GMP纳米平台、AI驱动的多组学建模，以及用于预测分析的联邦学习。通过整合肿瘤基因组学、免疫分析和先进递送技术，精准免疫肿瘤学有望提高口腔鳞状细胞癌的缓解率、持久性和生活质量。
Oral squamous cell carcinoma poses a significant global health burden, with over 370,000 annual cases and poor 5-year survival rates of 50%-60%, driven by risk factors like tobacco and alcohol. Despite advances in surgery, radiotherapy, and chemotherapy, functional morbidity and resistance necessitate precision immuno-oncology approaches. This review explores the tumour immune microenvironment in oral squamous cell carcinoma, characterized by immunosuppressive elements like M2 macrophages, myeloid-derived suppressor cells, and regulatory T cells, alongside spatial heterogeneity that complicates therapy. Biomarkers for patient selection include programmed death-ligand1 expression (via combined positive scoring), tumour mutational burden, neoantigen load, interferon-gamma-γ signatures, cytolytic scores, peripheral circulating tumour DNA, and single-cell/spatial profiling, though standardization remains critical. Immunotherapy has transformed oral squamous cell carcinoma management, with programmed cell death protein-1 inhibitors like nivolumab and pembrolizumab showing survival benefits in trials, particularly in programmed cell death protein-L1-positive cases. Emerging strategies encompass next-generation checkpoints (Lymphocyte activation gene-3, T-cell immunoreceptor with Ig and ITIM domains, OX40), personalized neoantigen vaccines, adoptive cell therapies (Tumour-Infiltrating Lymphocytes, Chimeric Antigen Receptor T-cell therapy), and rational combinations to counter resistance. Nanomedicine platforms-liposomes, polymeric nanoparticles, gold-based systems-enhance drug delivery, reprogram the Tumour and immune microenvironment, and enable chemo-immuno-photothermal synergies, addressing mucosal barriers and toxicity. Future priorities include biomarker validation via prospective registries, scalable Good Manufacturing Practice nanoplatforms, AI-driven multi-omic modeling, and federated learning for predictive analytics. By integrating tumour genomics, immune profiling, and advanced delivery, precision immuno-oncology holds promise to improve response rates, durability, and quality of life in oral squamous cell carcinoma.
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