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:From cold to hot: mechanisms of hyperthermia in modulating tumor immunology for enhanced immunotherapy.
From cold to hot: mechanisms of hyperthermia in modulating tumor immunology for enhanced immunotherapy.
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免疫疗法的出现彻底改变了癌症治疗,它利用免疫系统靶向恶性肿瘤,为传统疗法往往难以奏效的领域带来了新的希望。在此背景下,热疗(HT)作为一种有前景的辅助治疗手段重新受到关注,它能够增强放疗、化疗和免疫疗法的疗效。HT 影响固有免疫和适应性免疫系统,增强中性粒细胞、NK 细胞和树突状细胞等免疫细胞的活性,同时调节肿瘤微环境(TME)以促进免疫原性细胞死亡(ICD)并减少免疫抑制状态。这些效应有助于将免疫学上的“冷”肿瘤转化为“热”肿瘤,使其更易受到免疫介导的杀伤。
此外,HT 可以通过改善免疫细胞浸润、诱导损伤相关分子模式(DAMP)释放以及增强抗原呈递来放大免疫检查点抑制剂(ICI)的疗效。临床前和临床研究支持 HT 与 ICI 的联合应用,在原本耐药的肿瘤中显示出改善的结局。
然而,不同 HT 实施技术的完整治疗潜力仍有待充分理解,需要进一步研究以优化治疗方案、探索局部热疗与全身热疗的差异影响,并确定用于患者分层的生物标志物。本综述强调了 HT 在免疫中的多方面作用及其显著增强免疫疗法疗效的潜力。
The emergence of immunotherapies has revolutionized cancer treatment by leveraging the immune system to target malignancies, offering new hope where traditional therapies often fall short. Within this context, hyperthermia (HT) has re-emerged as a promising adjunctive treatment, capable of enhancing the effectiveness of radiotherapy, chemotherapy, and immunotherapy.
HT influences both the innate and adaptive immune systems, enhancing the activity of immune cells such as neutrophils, NK cells, and dendritic cells, while also modulating the tumor microenvironment (TME) to promote immunogenic cell death (ICD) and reduce immunosuppressive conditions. These effects contribute to the transformation of immunologically "cold" tumors into "hot" tumors, making them more susceptible to immune-mediated destruction.
Furthermore, HT can amplify the efficacy of immune checkpoint inhibitors (ICIs) by improving immune cell infiltration, inducing damage-associated molecular pattern (DAMP) release, and enhancing antigen presentation. Preclinical and clinical studies support the combination of HT with ICIs, demonstrating improved outcomes in otherwise resistant tumors.
However, the full therapeutic potential of the different technologies allowing to apply HT remains to be fully understood, and further research is needed to optimize treatment protocols, explore the differential impacts of local versus whole-body hyperthermia, and identify biomarkers for patient stratification. This review underscores the multifaceted role of HT in immunity and its potential to significantly enhance the efficacy of immunotherapy.
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