CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Improved Immunotherapy Efficacy by Vascular Modulation.
Improved Immunotherapy Efficacy by Vascular Modulation.
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癌症治疗中已开发多种调节肿瘤血管的策略,包括抗血管生成和血管正常化。血管调节可改变肿瘤微环境,例如改善氧合和免疫细胞浸润,因此适合与癌症疗法联合。免疫疗法的发展显著改善了癌症治疗,尤其有前景的包括免疫检查点阻断和CAR-T 细胞疗法:前者使用抗体阻断T细胞活化的负调控因子,后者则重编程T细胞以更好地靶向肿瘤抗原。然而,尽管部分晚期或转移性癌症患者已从免疫治疗中获益,真正应答者仍只占一部分。因此,有必要研究更好的疗效预测指标和克服耐药的方法。肿瘤内T细胞浸润不足或仅局限于肿瘤边缘,与免疫疗法应答不佳有关。考虑到(1)淋巴细胞募集需要白细胞与内皮细胞黏附,(2)血管系统控制肿瘤氧合,并在T细胞浸润和活化中发挥关键作用,将抗血管生成或血管正常化等血管靶向策略与免疫疗法联合,可能成为增强疗效的新方法。本文综述通过血管调节提高免疫疗法疗效的研究进展。
Several strategies have been developed to modulate the tumour vasculature for cancer therapy including anti-angiogenesis and vascular normalisation. Vasculature modulation results in changes to the tumour microenvironment including oxygenation and immune cell infiltration, therefore lending itself to combination with cancer therapy.
The development of immunotherapies has led to significant improvements in cancer treatment. Particularly promising are immune checkpoint blockade and CAR T cell therapies, which use antibodies against negative regulators of T cell activation and T cells reprogrammed to better target tumour antigens, respectively.
However, while immunotherapy is successful in some patients, including those with advanced or metastatic cancers, only a subset of patients respond.
Therefore, better predictors of patient response and methods to overcome resistance warrant investigation. Poor, or periphery-limited, T cell infiltration in the tumour is associated with poor responses to immunotherapy.
Given that (1) lymphocyte recruitment requires leucocyte-endothelial cell adhesion and (2) the vasculature controls tumour oxygenation and plays a pivotal role in T cell infiltration and activation, vessel targeting strategies including anti-angiogenesis and vascular normalisation in combination with immunotherapy are providing possible new strategies to enhance therapy.
Here, we review the progress of vessel modulation in enhancing immunotherapy efficacy.
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