Improved Immunotherapy Efficacy by Vascular Modulation.
Improved Immunotherapy Efficacy by Vascular Modulation.
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DOI：
10.3390/cancers13205207
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发表时间：
2021-10-17
期刊：
影响因子：
5.2
通讯作者：
Muñoz-Félix JM
中科院分区：
文献类型：
--
作者：
Newport EL;Pedrosa AR;Njegic A;Hodivala-Dilke KM;Muñoz-Félix JM
虽然近年来免疫疗法在癌症治疗方面取得了最高的改善率，但迫切需要进一步提高其疗效。许多策略旨在将无反应、免疫抑制的肿瘤转变为敏感的、免疫许可的肿瘤。肿瘤微环境的调节，特别是肿瘤血管的调节，为提高免疫治疗的敏感性提供了机会。肿瘤血管的调节可以增强肿瘤的氧合和T细胞的浸润。此外，肿瘤血管的成熟被认为与治疗剂的有效输送有关。本文综述了目前用于提高不同免疫疗法疗效的血管调节策略：PD-1/PD-L1和CTLA-4抗体、CAR T细胞和肿瘤疫苗。已经开发了几种策略来调节肿瘤血管系统用于癌症治疗，包括抗血管生成和血管正常化。血管调节导致肿瘤微环境的改变，包括氧合和免疫细胞的渗透，因此适合与癌症治疗相结合。免疫疗法的发展极大地改善了癌症的治疗。特别有希望的是免疫检查点阻断和CAR T细胞疗法，它们分别使用针对T细胞激活的负面调节因子的抗体和重新编程的T细胞，以更好地靶向肿瘤抗原。然而，尽管免疫疗法在一些患者中取得了成功，包括晚期或转移性癌症，但只有一小部分患者有反应。因此，更好地预测患者反应和克服耐药性的方法值得研究。肿瘤中T细胞浸润差或外周受限与免疫治疗反应差有关。鉴于(1)淋巴细胞募集需要白细胞-内皮细胞的黏附，(2)血管系统控制肿瘤的氧合，并在T细胞的渗透和激活中发挥关键作用，血管靶向策略，包括抗血管生成和血管正常化与免疫治疗相结合，为加强治疗提供了可能的新策略。在此，我们对血管调节在提高免疫治疗疗效方面的研究进展进行综述。
Although immunotherapy has given the highest rate of improvement in cancer treatment in recent years, there is an urgent need to further improve its efficacy. Numerous strategies aim to transform non-responsive, immunosuppressive tumours into sensitive, immunopermissive tumours. The modulation of the tumour microenvironment, and especially the tumour vasculature offers opportunities for improved sensitivity to immunotherapy. Modulation of tumour blood vessels can enhance tumour oxygenation and T cell infiltration. Additionally, maturation of tumour blood vessels is thought to be involved in the efficient delivery of therapeutic agents. This review compiles the current strategies of vascular modulation to improve the efficacy of different immunotherapies: PD-1/PD-L1 and CTLA-4 antibodies, CAR T cells and cancer vaccines. 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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影响因子：
17.1
作者：
Allen E;Jabouille A;Rivera LB;Lodewijckx I;Missiaen R;Steri V;Feyen K;Tawney J;Hanahan D;Michael IP;Bergers G
通讯作者：
Bergers G
影响因子：
2.2
作者：
Bose A;Lowe DB;Rao A;Storkus WJ
通讯作者：
Storkus WJ
影响因子：
64.5
作者：
BROOKS, PC;MONTGOMERY, AMP;CHERESH, DA
通讯作者：
CHERESH, DA
IV期或复发性非小细胞肺癌中的一线Nivolumab。
DOI：
10.1056/nejmoa1613493
发表时间：
2017-06-22
期刊：
The New England journal of medicine
影响因子：
--
作者：
Carbone DP;Reck M;Paz-Ares L;Creelan B;Horn L;Steins M;Felip E;van den Heuvel MM;Ciuleanu TE;Badin F;Ready N;Hiltermann TJN;Nair S;Juergens R;Peters S;Minenza E;Wrangle JM;Rodriguez-Abreu D;Borghaei H;Blumenschein GR Jr;Villaruz LC;Havel L;Krejci J;Corral Jaime J;Chang H;Geese WJ;Bhagavatheeswaran P;Chen AC;Socinski MA;CheckMate 026 Investigators
通讯作者：
CheckMate 026 Investigators
影响因子：
51.1
作者：
Altorki, Nasser K.;McGraw, Timothy E.;Formenti, Silvia C.
通讯作者：
Formenti, Silvia C.