RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Harnessing chitosan-based biomaterials for advanced cancer immunotherapy: from nanocarriers to tumor microenvironment modulation.
Harnessing chitosan-based biomaterials for advanced cancer immunotherapy: from nanocarriers to tumor microenvironment modulation.
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癌症免疫治疗已经改变了肿瘤学领域,然而,其临床疗效仍然受到免疫抑制性肿瘤微环境(TME)、治疗递送不佳、全身毒性以及治疗耐药性的限制。壳聚糖是一种具有生物相容性和可生物降解性的多糖,已作为一种多功能生物材料出现,能够通过其内在的免疫调节活性和先进的药物递送功能来应对这些挑战。本综述总结了基于壳聚糖的生物材料在癌症免疫治疗中的最新进展,重点强调其通过涉及模式识别受体、环鸟苷酸-腺苷酸合成酶(cGAS)=干扰素基因刺激因子(STING)信号通路、树突状细胞(DCs)、巨噬细胞、自然杀伤(NK)细胞和T淋巴细胞的途径激活先天性和适应性免疫应答的能力。本文讨论了基于壳聚糖的纳米颗粒和水凝胶作为递送细胞因子、核酸、免疫佐剂、癌症疫苗和免疫检查点治疗药物的平台的设计与应用。特别关注了它们在TME重塑、局部持续药物释放、术后免疫治疗以及整合化疗、放疗(RT)、光疗和免疫治疗的联合方法中的作用。还讨论了新兴策略,包括刺激响应系统、仿生制剂和多功能纳米平台。
最后,我们讨论了当前的转化挑战和未来前景,强调基于壳聚糖的生物材料在增强抗肿瘤免疫和改善癌症免疫治疗临床结局方面的潜力。
Cancer immunotherapy has transformed oncology, however, its clinical efficacy remains limited by immunosuppressive tumor microenvironments (TMEs), poor therapeutic delivery, systematic toxicity, treatment resistance. Chitosan, a biocompatible and biodegradable polysaccharide, has emerged as a versatile biomaterial capable of addressing these challenges through both intrinsics immunomodulatory activity and advanced drug-delivery functions. This review summarizs recent advances in chitosan-based biomaterials for cancer immunotherapy, highlighting their ability to activate innate and adaptive immune responses through pathways involving patterns recognition receptors, cyclic GMP-AMP synthase (cGAS)=simulator of interferon genes (STING) signaling, dendric cells (DCs)macrophages, natural killer (NK) cells and T lymphocytes.
The design and application of chitosan-based nanoparticles and hydrogels as platformsfor delivering cytokines, nucleic acids, immune adjuvant, cancer vaccines and immune checkpoint therapeutics are discussed.
Particular attention is given to their roles in TME remodeling, sustained local drug release, postsurgical immunotherapy, and combination approaches that integrate chemotherapy, radiotherapy (RT), phototherapy and immunotherapy. Emerging strategies, including stimuli-responsive systems, biomimetic formulations, and multifunctional nanoplatforms are also discussed.
Finally, we discuss the current translational current translational challenges and future perspectives, emphasizing the potential of chitosan-based biomaterials to enhance antitumor immunity and improve clinical outcomes in cancer immunotherapy.
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