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Spatiotemporal Dynamics of Intratumoral Immune Cells Reveal the Immune Landscape in Human Cancer

Gabriela Bindea, Bernhard Mlecnik, Marie Tosolini, Amos Kirilovsky, Maximilian Waldner, Anna C Obenauf, Helen Angell, Tessa Fredriksen, Lucie Lafontaine, Anne Berger, Patrick Bruneval, Wolf Herman Fridman, etc.

Immunity. 2013 Oct 17;39(4):782-95.

PMID: 24138885

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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
IAR42413381 Interleukin-21 from mouse Interleukin-21 from mouse Price
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