免疫系统
生物
肿瘤进展
肿瘤微环境
结直肠癌
趋化因子
免疫学
癌症
肿瘤发生
先天免疫系统
癌症研究
癌变
遗传学
作者
Gabriela Bindea,Bernhard Mlecnik,Marie Tosolini,Amos Kirilovsky,Maximilian J. Waldner,Anna C. Obenauf,Helen K. Angell,Tessa Fredriksen,Lucie Lafontaine,Anne Berger,Patrick Bruneval,Wolf–Herman Fridman,Christoph Becker,Franck Pagès,Michael R. Speicher,Zlatko Trajanoski,Jérôme Galon
出处
期刊:Immunity
[Elsevier]
日期:2013-10-01
卷期号:39 (4): 782-795
被引量:2805
标识
DOI:10.1016/j.immuni.2013.10.003
摘要
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.
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