一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
这些发现支持采用多靶点CAR-T 策略来应对NSCLC及可能其他实体瘤中的抗原异质性。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Cryoablation plus chemotherapy regimen enhance anti-tumor immune response in a mouse model of Lewis lung cancer.
Cryoablation plus chemotherapy regimen enhance anti-tumor immune response in a mouse model of Lewis lung cancer.
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冷冻+化疗能有效抑制肺癌生长、延长生存期并激活免疫反应,为联合治疗提供了理论依据。如何长期维持免疫反应是下一步需要解决的问题。
冷冻消融(cryo)是一种局部抗肿瘤方法,其机制之一是激活免疫,但受多种因素影响。大量研究证明,基于cryo的联合治疗能更有效地协同激活免疫。cryo联合化疗(chemo)已被证明可改善肿瘤患者的生活质量并延长生存期,但其免疫效应仍不明确。
建立C57B/L6小鼠肺癌皮下移植瘤模型,于干预后两个时间点处死。我们观察了冷冻+化疗对生存时间、肿瘤生长以及免疫细胞和细胞因子动态变化的影响。
冷冻+化疗不仅能显著延长小鼠的生存期、抑制肿瘤生长、降低肿瘤细胞的增殖活性,还能更有效地促进免疫反应。冷冻+化疗可增加脾脏和肿瘤微环境中的CD4+ T细胞数量,减少肿瘤微环境中Treg细胞的浸润。此外,冷冻+化疗可提高IL-2和IFN-γ的表达水平,降低TGF-β的水平。然而,值得注意的是,免疫促进作用随时间逐渐减弱。
Cryoablation (cryo) is a local anti-tumor method and activation of immunity is one of its mechanisms, but it is affected by many factors. Numerous studies have proved that combination therapy based on cryo can activate immunity more effectively and synergistically. Cryo combined with chemotherapy(chemo) has been proven to improve the quality of life and prolong survival of tumor patients, but the immune effect is still unclear.
C57B/L6 mouse lung cancer subcutaneous transplanted tumor model was established and sacrificed at two time points after intervention. We observed the effects of cryo + chemo on survival time, tumor growth, and dynamic changes of immune cells and cytokines.
Cryo + chemo could not only significantly prolong the survival period of mice, inhibit tumor growth and reduce the proliferation activity of tumor cells, but also promote immune response more effectively. Cryo + chemo could increase the number of CD4 + T cells both in spleen and tumor microenvironment, decrease the infiltration of Treg cells in the tumor microenvironment. Besides, cryo + chemo could increase the expression levels of IL-2 and IFN-γ, and reduce the levels of TGF-β. However, it is worth noting that the immune-promoting effect gradually decreases over time.
Cryo + chemo can effectively inhibit the growth of lung cancer, prolong the survival period and activate the immune response, providing a theoretical basis for the combined treatment. How to maintain the immune response for a long time is the next problem to be solved.
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