Newport Emma L, Pedrosa Ana Rita, Njegic Alexandra, Hodivala-Dilke Kairbaan M, Muñoz-Félix José M
Centre for Tumour Microenvironment, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Department of Biochemistry and Molecular Biology, Institute of Biomedical Research of Salamanca (IBSAL), Universidad de Salamanca Spain, 37007 Salamanca, Spain.
Cancers (Basel). 2021 Oct 17;13(20):5207. doi: 10.3390/cancers13205207.
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.
已经开发了几种策略来调节肿瘤血管系统以进行癌症治疗，包括抗血管生成和血管正常化。血管系统调节会导致肿瘤微环境发生变化，包括氧合作用和免疫细胞浸润，因此适合与癌症治疗联合使用。免疫疗法的发展已使癌症治疗取得了显著进展。特别有前景的是免疫检查点阻断疗法和嵌合抗原受体（CAR）T细胞疗法，它们分别使用针对T细胞激活负调节因子的抗体和经过重新编程以更好地靶向肿瘤抗原的T细胞。然而，尽管免疫疗法在一些患者中取得了成功，包括那些患有晚期或转移性癌症的患者，但只有一部分患者有反应。因此，需要研究更好的患者反应预测指标和克服耐药性的方法。肿瘤中T细胞浸润不良或局限于周边与免疫疗法反应不佳有关。鉴于（1）淋巴细胞募集需要白细胞与内皮细胞粘附，以及（2）血管系统控制肿瘤氧合作用并在T细胞浸润和激活中起关键作用，包括抗血管生成和血管正常化在内的血管靶向策略与免疫疗法联合使用正提供增强治疗效果的可能新策略。在此，我们综述血管调节在提高免疫疗法疗效方面的进展。
