Spatiotemporal Dynamics of Intratumoral Immune Cells Reveal the Immune Landscape in Human Cancer
Spatiotemporal Dynamics of Intratumoral Immune Cells Reveal the Immune Landscape in Human Cancer
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DOI：
10.1016/j.immuni.2013.10.003
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发表时间：
2013-10-17
期刊：
影响因子：
32.4
通讯作者：
Galon, Jerome
中科院分区：
文献类型：
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作者：
Bindea, Gabriela;Mlecnik, Bernhard;Galon, Jerome
肿瘤与微环境之间的复杂相互作用尚待阐明。结合大规模方法，我们检查了28种不同的免疫细胞类型（免疫组）浸润肿瘤的时空动力学。我们发现，免疫浸润成分在每个肿瘤阶段都发生了变化，并且特定细胞对生存有重大影响。 T卵泡辅助器（TFH）细胞和先天细胞的密度增加，而大多数T细胞密度随肿瘤进展而降低。 B细胞的数量是核心免疫网络中的关键参与者，并且与长时间的生存有关，在后期增加，对复发和肿瘤进展产生双重影响。在三个内窥镜原位结肠癌小鼠模型中证明了免疫控制相关性。趋化因子CXCL13的基因组不稳定性是与TFH和B细胞浸润相关的机制。 CXCL13和IL21是与存活相关的TFH/B细胞轴的关键因子。这项综合研究揭示了人类结直肠癌的免疫景观以及与肿瘤进展和复发有关的微环境的主要标志。
The complex interactions between tumors and their microenvironment remain to be elucidated. Combining large-scale approaches, we examined the spatio-temporal dynamics of 28 different immune cell types (immunome) infiltrating tumors. We found that the immune infiltrate composition changed at each tumor stage and that particular cells had a major impact on survival. Densities of T follicular helper (Tfh) cells and innate cells increased, whereas most T cell densities decreased along with tumor progression. The number of B cells, which are key players in the core immune network and are associated with prolonged survival, increased at a late stage and showed a dual effect on recurrence and tumor progression. The immune control relevance was demonstrated in three endoscopic orthotopic colon-cancer mouse models. Genomic instability of the chemokine CXCL13 was a mechanism associated with Tfh and B cell infiltration. CXCL13 and IL21 were pivotal factors for the Tfh/B cell axis correlating with survival. This integrative study reveals the immune landscape in human colorectal cancer and the major hallmarks of the microenvironment associated with tumor progression and recurrence.