Behavior of immune players in the tumor microenvironment.
Behavior of immune players in the tumor microenvironment.
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DOI：
10.1097/cco.0b013e32831bc38a
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发表时间：
2009-01
影响因子：
3.4
通讯作者：
Pittet MJ
中科院分区：
文献类型：
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作者：
Pittet MJ
肿瘤招募了各种免疫细胞，它们的功能似乎截然不同。然而，这些细胞在原位的确切作用仍然非常未知。这篇综述介绍了一项新的发现，利用活体成像直接研究组织中的免疫玩家。识别同源抗原肽的细胞毒性T淋巴细胞(CTL)可以从周围向中心渗透肿瘤，并物理地结合和清除呈递抗原的肿瘤细胞。然而，报道的CTL体内杀伤肿瘤细胞的动力学令人惊讶地低，因为一个CTL需要几个小时才能消除一个肿瘤细胞。此外，T调节(Treg)细胞可以创造一个抑制环境，限制CTL细胞毒颗粒的释放，从而保护肿瘤细胞不被杀死。在与肿瘤相关巨噬细胞(TAM)的长时间相互作用中，CTL可能会进一步被颠覆。最后，TAMs可以通过在血管附近募集肿瘤细胞并促进它们的血管内转移来直接促进肿瘤的侵袭。活体成像已经开始揭示与肿瘤相关的免疫事件，因为它们在体内展开。在接下来的几年里，这项技术应该被利用来进一步剖析肿瘤微环境，并确定增强抗肿瘤免疫的治疗方法。
Tumors recruit various immune cells with seemingly contrasting functions. Yet, the precise role of these cells in situ remains vastly unknown. This review presents a new discovery effort that employs intravital imaging to study immune players directly in tissues. Cytotoxic T lymphocytes (CTLs) that recognize cognate antigenic peptide can infiltrate tumors from the periphery to the center, and physically engage and eliminate antigen-presenting tumor cells. Nevertheless, the reported kinetics for tumor cell killing by CTLs in vivo is surprisingly low as it takes several hours for one CTL to eliminate one tumor cell. Also, T regulatory (Treg) cells can create a suppressive milieu that restricts the release of CTL cytotoxic granules, which protects tumor cells from being killed. CTLs may be further subverted during lengthy interactions with tumor-associated macrophages (TAMs). Finally, TAMs can directly facilitate tumor invasion by recruiting tumor cells nearby vessels and promoting their intravasation. Intravital imaging has started to uncover tumor-related immune events as they unfold in vivo. The technology should be exploited in the coming years to dissect further the tumor microenvironment and to define therapeutics that augment antitumor immunity.