肿瘤细胞治疗研究
英文原题：Beta-glucans in oncology: revolutionizing treatment with immune power & tumor targeting.
Beta-glucans in oncology: revolutionizing treatment with immune power & tumor targeting.
临床试验（2023-2025）显示出显著的生存获益，例如黑色素瘤（风险比[HR] 0.65，95% CI 0.48-0.87）和肺癌（HR 0.72，95% CI 0.55-0.94）的总生存期（OS）改善，同时化疗毒性降低。
β-葡聚糖是天然存在的多糖，来源于真菌、酵母、谷物和细菌，因其多方面的免疫调节、抗炎和直接抗肿瘤特性，已成为强效的癌症治疗药物。这些化合物与模式识别受体（PRRs）如 Dectin-1、Toll 样受体（TLRs）和补体受体 3（CR3）结合，激活巨噬细胞、自然杀伤（NK）细胞和树突状细胞，从而增强抗肿瘤免疫。β-葡聚糖抑制促炎细胞因子（如 TNF-α、IL-6）和肿瘤促进通路如 NF-κB，同时调节调节性 T 细胞（Tregs）并下调 PD-L1 以克服免疫逃逸。它们通过 Bax/Bcl-2 调控诱导凋亡，将细胞周期阻滞在 G1/S 或 G2/M 期，并通过靶向 VEGF 和 MMPs 抑制血管生成。临床试验（2023-2025）显示显著的生存获益，例如改善黑色素瘤的总生存期（OS）（风险比 [HR] 0.65，95% CI 0.48-0.87）和肺癌（HR 0.72，95% CI 0.55-0.94），同时降低化疗毒性。与 PD-1/PD-L1 抑制剂的协同作用增强免疫治疗疗效，特别是在免疫原性肿瘤中。先进的纳米递送系统，包括胶束和外泌体，改善生物利用度和肿瘤靶向性。然而，生物利用度可变、剂量不一致、副作用（如 10-15% 患者出现胃肠道不适，2-5% 出现过敏反应）以及不同肿瘤类型间疗效数据矛盾等挑战，需要进一步研究。本综述整合了 β-葡聚糖的作用机制、临床证据、递送创新和挑战，将其定位为精准肿瘤学中有前景的辅助治疗手段。
Beta-glucans, naturally occurring polysaccharides derived from fungi, yeasts, cereals, and bacteria, have emerged as potent cancer therapeutics due to their multifaceted immunomodulatory, anti-inflammatory, and direct anti-tumor properties. These compounds engage pattern recognition receptors (PRRs) such as Dectin-1, Toll-like receptors (TLRs), and complement receptor 3 (CR3), activating macrophages, natural killer (NK) cells, and dendritic cells to enhance anti-tumor immunity. Beta-glucans suppress pro-inflammatory cytokines (e.g., TNF-α, IL-6) and tumor-promoting pathways like NF-κB, while modulating T-regulatory cells (Tregs) and downregulating PD-L1 to overcome immune evasion. They induce apoptosis via Bax/Bcl-2 regulation, arrest cell cycles at G1/S or G2/M phases, and inhibit angiogenesis by targeting VEGF and MMPs. Clinical trials (2023-2025) demonstrate significant survival benefits, such as improved overall survival (OS) in melanoma (hazard ratio [HR] 0.65, 95% CI 0.48-0.87) and lung cancer (HR 0.72, 95% CI 0.55-0.94), alongside reduced chemotherapy toxicity. Synergy with PD-1/PD-L1 inhibitors enhances immunotherapy efficacy, particularly in immunogenic tumors. Advanced nano-delivery systems, including micelles and exosomes, improve bioavailability and tumor targeting. However, challenges like variable bioavailability, dosing inconsistencies, side effects (e.g., gastrointestinal discomfort in 10-15% of patients, allergic reactions in 2-5%), and conflicting efficacy data across tumor types necessitate further research. This review consolidates beta-glucan mechanisms, clinical evidence, delivery innovations, and challenges, positioning them as promising adjuncts in precision oncology.
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