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. 2013 Oct 17;39(4):782-95.
doi: 10.1016/j.immuni.2013.10.003.

Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer

Gabriela Bindea  1 , Bernhard Mlecnik, Marie Tosolini, Amos Kirilovsky, Maximilian Waldner, Anna C Obenauf, Helen Angell, Tessa Fredriksen, Lucie Lafontaine, Anne Berger, Patrick Bruneval, Wolf Herman Fridman, Christoph Becker, Franck Pagès, Michael R Speicher, Zlatko Trajanoski, Jérôme Galon
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Free article

Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer

Gabriela Bindea et al. Immunity. .
Free article

Abstract

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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