Antiangiogenic therapy improves the antitumor effect of adoptive cell immunotherapy by normalizing tumor vasculature
Antiangiogenic therapy improves the antitumor effect of adoptive cell immunotherapy by normalizing tumor vasculature
复制标题
抗血管生成疗法通过使肿瘤脉管系统正常化来提高过继性细胞免疫疗法的抗肿瘤效果
DOI：
10.1007/s12032-013-0698-1
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发表时间：
2013-12-01
期刊：
影响因子：
3.4
通讯作者：
Huang, Guichun
中科院分区：
文献类型：
--
作者：
Shi, Shujing;Chen, Longbang;Huang, Guichun
异常的肿瘤脉管系统和随后的肿瘤缺氧通过阻碍细胞毒性T细胞归巢到肿瘤实质中并抑制其抗肿瘤功效而促成肿瘤细胞的免疫耐受。这些障碍可能解释了为什么过继细胞免疫疗法的前景不发挥显着的抗肿瘤活性。缺氧通过激活缺氧诱导因子（HIF-1）和血管内皮生长因子途径而有助于免疫抑制，其在促进肿瘤细胞生长和存活中起决定性作用。肿瘤缺氧通过炎性细胞向免疫抑制表型（如髓源性抑制细胞、肿瘤相关巨噬细胞和树突状细胞）的积累和随后的极化产生免疫抑制微环境。抗血管生成治疗可以使肿瘤血管正常化，减少缺氧肿瘤面积，因此可能是一种有效的增强免疫治疗的方式。单独的免疫细胞免疫疗法不足以有效地减少肿瘤生长，因为其抗肿瘤作用被免疫抑制性缺氧肿瘤微环境抑制。本文综述了抗血管生成治疗与过继性细胞免疫治疗的联合应用可发挥协同抗肿瘤作用，为今后的抗肿瘤治疗提供参考。
Abnormal tumor vasculature and subsequent tumor hypoxia contribute to immune tolerance of tumor cells by impeding the homing of cytotoxic T cells into tumor parenchyma and inhibiting their antitumor efficacy. These obstacles might explain why the promising approach of adoptive cell immunotherapy does not exert significant antitumor activity. Hypoxia contributes to immune suppression by activating hypoxia-inducible factor (HIF-1) and the vascular endothelial growth factor pathway, which plays a determining role in promoting tumor cell growth and survival. Tumor hypoxia creates an immunosuppressive microenvironment via the accumulation and subsequent polarization of inflammatory cells toward immune suppression phenotypes, such as myeloid-derived suppressor cells, tumor-associated macrophages, and dendritic cells. Antiangiogenic therapy could normalize tumor vasculature and decrease hypoxic tumor area and thus may be an effective modality to potentiate immunotherapy. Adoptive cell immunotherapy alone is not efficient enough to decrease tumor growth as its antitumor effect is inhibited by the immunosuppressive hypoxic tumor microenvironment. This review describes that combination of antiangiogenic therapy with adoptive cell immunotherapy can exert synergistic antitumor effect, which will contribute to improve strategies for future anticancer therapies.