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:Grain-sized moxibustion activates dendritic cells to enhance the antitumor immunity of cancer vaccines.
Grain-sized moxibustion activates dendritic cells to enhance the antitumor immunity of cancer vaccines.
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gM 和 β 受体阻滞剂均通过抑制 β 肾上腺素能和促进 DC 成熟来增强癌症疫苗的疗效。
艾灸是一种传统中医疗法,通过燃烧艾(Artemisia argyi H.L. v. & Vaniot)产生的热刺激穴位,治疗传统上与免疫功能障碍和慢性炎症相关的“虚寒证”。现代药理学研究显示,麦粒灸(gM)可增强自然杀伤(NK)细胞募集等先天免疫监视功能。然而,其与疫苗诱导的适应性免疫之间是否存在协同作用尚未探究。遵循中医“扶正祛邪”原则,本研究探讨gM能否增强癌症疫苗疗效,并验证穴位热刺激放大适应性抗肿瘤免疫的机制基础。
在荷瘤小鼠模型中,对足三里(ST36)穴施行麦粒灸。通过流式细胞术、β肾上腺素能受体阻断和细胞清除实验评估其对癌症疫苗的佐剂作用。
麦粒灸与癌症疫苗协同,显著抑制肿瘤生长。机制上,麦粒灸抑制β肾上腺素能信号,促进树突状细胞(DC)成熟,并进一步协调CD4+ T细胞、CD8+ T细胞和NK细胞应答。CD4+ T细胞是主要效应细胞,NK细胞发挥次要作用。普萘洛尔可模拟麦粒灸效果;与疫苗联合时,进一步增强DC活化和肿瘤抑制。
麦粒灸和β受体阻滞剂均可通过抑制β肾上腺素能信号并促进DC成熟,提高癌症疫苗疗效。这些发现从机制上连接了中医“扶正祛邪”策略与现代免疫疗法,并将β肾上腺素能调节定位为传统和药理干预的共同靶点。
Moxibustion, a traditional Chinese medicine (TCM) therapy, employs thermal stimulation from the combustion of Artemisia argyi H.L v. & Vaniot at acupoints to treat "deficiency-cold syndromes" (xuhan zheng), historically linked to immune dysfunction and chronic inflammation. Modern pharmacological studies showed that grain-sized moxibustion (gM) enhances innate immune surveillance such as natural killer (NK) cell recruitment. However, its synergy with vaccine-induced adaptive immunity remains unexplored. Guided by the TCM principle of fu zheng qu xie ("fortify the host to dispel pathogens"), this study investigated whether gM augments cancer vaccine efficacy and validate the mechanistic basis of thermal acupoint stimulation in amplifying adaptive antitumor immunity.
In tumor-bearing mice model, gM was applied to the ST36 (Zusanli) acupoint. Adjuvant effects on the cancer vaccine were evaluated through flow cytometry, -adrenergic receptor blockade, and cell depletion.
gM synergized with the cancer vaccine, significantly suppressing tumor growth. Mechanistically, gM inhibited -adrenergic signaling, driving DC maturation and subsequent coordination of CD4 + T cell, CD8 + T cell and NK cell responses. CD4 + T cells as primary effectors, with NK cells playing a secondary role. Propranolol mirrored gM's effects, further enhancing DC activation and tumor suppression when combined with vaccination.
Both gM and -blockers enhance cancer vaccine efficacy through -adrenergic suppression and maturation of DC. These findings mechanistically bridge TCM's fu zheng qu xie strategy with modern immunotherapy, positioning -adrenergic modulation as a convergent target for traditional and pharmacological interventions.
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