CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Intelligent photothermal dendritic cells restart the cancer immunity cycle through enhanced immunogenic cell death.
Intelligent photothermal dendritic cells restart the cancer immunity cycle through enhanced immunogenic cell death.
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树突状细胞(DCs)在启动抗原特异性肿瘤免疫中发挥关键作用。然而,由于免疫抑制性肿瘤微环境(TME)导致DCs功能异常,以及肿瘤浸润DCs数量不足,可促进免疫耐受和肿瘤免疫逃逸。因此,利用DCs诱导高效抗肿瘤免疫具有巨大潜力。本文中,我们开发了智能DCs(iDCs),其由负载光热剂(IR-797)并被成熟DC膜包覆的纳米颗粒组成。iDCs表面的DC细胞膜保留了呈递抗原和致敏T细胞的能力。iDCs还可进入淋巴结并刺激T细胞。活化的T细胞降低了肿瘤细胞中热休克蛋白(HSPs)的表达,使其对热应激更加敏感。随后,我们使用温和光热治疗(42-45 °C)诱导免疫原性细胞死亡,并促成协同抗肿瘤效应。iDCs作为一种精细且精确的系统,与基于DC的免疫治疗和热疗相结合,可长期大规模储存,因此可应用于众多患者。
Dendritic cells (DCs) play a pivotal role in initiating antigen-specific tumor immunity.
However, the abnormal function of DCs owing to the immunosuppressive tumor microenvironment (TME) and the insufficient number of tumor infiltrating DCs could promote immune tolerance and tumor immune escape.
Thus, there is great potential to employ DCs to induce efficient antitumor immunity. In this paper, we developed intelligent DCs (iDCs), which consist of nanoparticles loaded with photothermal agents (IR-797) and coated with a mature DC membrane. The DC cell membrane on the surface of iDCs preserves the ability to present antigens and prime T cells. The iDCs can also enter the lymph node and stimulate T cells.
The activated T cells reduced the expression of heat shock proteins (HSPs) in tumor cells, rendering them more sensitive to heat stress. Subsequently, we used mild photothermal therapy (42-45 °C) to induce immunogenic cell death and contribute to a synergistic antitumor effect. iDCs as a refined and precise system in combination with DC-based immunotherapy and thermal therapy can be stored long-term and on a large scale, so they can be applied in many patients.
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