Overcoming physical stromal barriers to cancer immunotherapy.
Overcoming physical stromal barriers to cancer immunotherapy.
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DOI：
10.1007/s13346-021-01036-y
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发表时间：
2021-12
影响因子：
5.4
通讯作者：
Suk JS
中科院分区：
文献类型：
--
作者：
Chung SW;Xie Y;Suk JS
免疫疗法已经成为治疗臭名昭著的难治性癌症的前所未有的希望。许多研究药物和免疫疗法--包括联合疗法--正在进行临床前和临床研究。然而，由于存在几种耐药机制，在不同类型的癌症中只有一小部分患者对治疗有反应。已经做出了广泛的努力来克服这一限制，并扩大可以从这种最先进的治疗方式中受益的患者群体。在耐药性的各种原因中，我们在这里重点关注阻碍免疫治疗药物分子和/或天然和工程免疫细胞与癌症组织和细胞接触的物理基质屏障。导致耐药性的两个主要基质屏障包括异常的肿瘤血管和过度的细胞外基质积聚，它们分别限制了分子和细胞免疫治疗剂向肿瘤组织的外渗和渗透。在这里，我们回顾了这些限制免疫治疗疗效的障碍的特点，并讨论了可能有助于免疫治疗克服这些障碍并改善治疗结果的最新进展。
Immunotherapy has emerged as an unprecedented hope for the treatment of notoriously refractory cancers. Numerous investigational drugs and immunotherapy-including combination regimens are under preclinical and clinical investigation. However, only a small patient subpopulation across different types of cancer responds to the therapy due to the presence of several mechanisms of resistance. There have been extensive efforts to overcome this limitation and to expand the patient population that could be benefited by this state-of-the-art therapeutic modality. Among various causes of the resistance, we here focus on physical stromal barriers that impede the access of immunotherapeutic drug molecules and/or native and engineered immune cells to cancer tissues and cells. Two primary stromal barriers that contribute to the resistance include aberrant tumor vasculatures and excessive extracellular matrix build-ups that restrict extravasation and infiltration, respectively, of molecular and cellular immunotherapeutic agents into tumor tissues. Here, we review the features of these barriers that limit the efficacy of immunotherapy and discuss recent advances that could potentially help immunotherapy overcome the barriers and improve therapeutic outcomes.
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影响因子：
18.9
作者：
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6
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影响因子：
6.2
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影响因子：
82.9
作者：
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通讯作者：
Krummel MF