Ways to enhance lymphocyte trafficking into tumors and fitness of tumor infiltrating lymphocytes.
Ways to enhance lymphocyte trafficking into tumors and fitness of tumor infiltrating lymphocytes.
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DOI：
10.3389/fonc.2013.00231
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发表时间：
2013-09-11
影响因子：
4.7
通讯作者：
Calcinotto A
中科院分区：
文献类型：
--
作者：
Bellone M;Calcinotto A
肿瘤是T淋巴细胞的不利微环境。事实上，不规则血流和内皮细胞（EC）无能的特点，大多数实体瘤阻碍白细胞粘附，外渗和浸润。此外，癌细胞内的缺氧和能量代谢的重编程在限制T细胞的存活和效应子功能的恶劣环境中转化肿瘤块，无论是通过疫苗接种在体内诱导还是过继转移。在这篇综述中，我们将总结在我们的理解肿瘤相关的新生血管的特点，以及肿瘤的代谢，可能会影响T细胞的运输和健身的肿瘤浸润淋巴细胞的最新进展。特别是，我们将集中在如何在肿瘤EC的特性的知识的进步，使识别策略，以正常化的肿瘤血管系统和/或克服EC无能，从而增加白细胞血管壁的相互作用和淋巴细胞浸润的肿瘤。我们还将专注于作用于细胞及其释放分子的药物，以暂时使肿瘤微环境更适合肿瘤浸润性T淋巴细胞，从而提高主动和过继免疫疗法的治疗效果。
The tumor is a hostile microenvironment for T lymphocytes. Indeed, irregular blood flow, and endothelial cell (EC) anergy that characterize most solid tumors hamper leukocyte adhesion, extravasation, and infiltration. In addition, hypoxia and reprograming of energy metabolism within cancer cells transform the tumor mass in a harsh environment that limits survival and effector functions of T cells, regardless of being induced in vivo by vaccination or adoptively transferred. In this review, we will summarize on recent advances in our understanding of the characteristics of tumor-associated neo-angiogenic vessels as well as of the tumor metabolism that may impact on T cell trafficking and fitness of tumor infiltrating lymphocytes. In particular, we will focus on how advances in knowledge of the characteristics of tumor ECs have enabled identifying strategies to normalize the tumor-vasculature and/or overcome EC anergy, thus increasing leukocyte-vessel wall interactions and lymphocyte infiltration in tumors. We will also focus on drugs acting on cells and their released molecules to transiently render the tumor microenvironment more suitable for tumor infiltrating T lymphocytes, thus increasing the therapeutic effectiveness of both active and adoptive immunotherapies.