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.
肿瘤细胞治疗研究
英文原题:Cytokine-based immunotherapy for gastric cancer: targeting inflammation for tumor control.
Cytokine-based immunotherapy for gastric cancer: targeting inflammation for tumor control.
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新兴的癌症免疫治疗方法,尤其是基于细胞因子的方法,通过改变免疫系统对肿瘤细胞的炎症反应,可能有助于减缓胃癌进展。细胞因子是在免疫细胞之间传递信号的微小信号蛋白,可能促进或抑制癌症生长。促炎细胞因子促进肿瘤发展,而抗肿瘤细胞因子帮助宿主排斥癌细胞。
本研究探讨了针对胃癌促炎和抗肿瘤免疫反应的细胞因子靶向方法。研究人员希望通过递送 IL-2、IFNs 和 TNF-α 等细胞因子来激活炎症通路并对抗肿瘤,从而重新激活 CTLs 和 NK 细胞等免疫细胞。由于细胞因子具有显著的多效性作用,其治疗应用较为困难,可能引起过度的全身性炎症或免疫抑制。本综述涵盖了合成细胞因子、细胞因子偶联物及其局部给药的最新进展,这些进展旨在提高治疗指数:增强杀伤癌细胞的潜力,同时尽量减少脱靶损伤。
该研究考察了细胞因子与 TME 之间的关系,揭示了 IL-10 和 TGF-β 等免疫抑制性细胞因子在促进免疫逃逸表型中的作用。这些结果表明,抑制性通路靶向治疗与基于细胞因子的治疗可能克服耐药机制。基于细胞因子的免疫疗法与免疫检查点抑制剂联合,预计将改变胃癌治疗格局并重塑肿瘤免疫微环境动态,恢复抗肿瘤免疫。来自当前临床研究的综合数据将有助于确定这些治疗在胃癌中的地位。
Emerging cancer immunotherapy methods, notably cytokine-based ones that modify immune systems' inflammatory reactions to tumor cells, may help slow gastric cancer progression. Cytokines, tiny signaling proteins that communicate between immune cells, may help or hinder cancer growth. Pro-inflammatory cytokines encourage tumor development, whereas antitumor ones help the host reject cancer cells.
This study considers cytokine-targeted methods for gastric cancer pro-inflammatory and antitumor immune responses. Researchers want to renew immune cells like cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells by delivering cytokines like interleukin-2 (IL-2), interferons (IFNs), and tumor necrosis factor-alpha (TNF-α) to activate inflammatory pathways and combat tumors. Since cytokines have significant pleiotropic effects, their therapeutic use is difficult and may cause excessive systemic inflammation or immunological suppression. This review covers current advancements in synthetic cytokines, cytokine-conjugates, and local administration of these aimed to enhance the therapeutic index: increase the potential to kill cancer cells while minimizing off-target damage.
The study examines the relationship between cytokines and tumor microenvironment (TME), revealing the role of immunosuppressive cytokines like IL-10 and transforming growth factor-beta (TGF-β) in promoting an immune-evasive phenotype. These results suggest that inhibitory pathway targeting, and cytokine-based therapy may overcome resistance mechanisms.
Cytokine-based immunotherapies combined with immune checkpoint inhibitors are predicted to change gastric cancer therapy and rebuild tumor-immune microenvironment dynamics, restoring antitumor immunity. Comprehensive data from current clinical studies will assist in establishing the position of these treatments in gastric cancer.
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