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Bindea, G; Mlecnik, B; Tosolini, M; Kirilovsky, A; Waldner, M; Obenauf, AC; Angell, H; Fredriksen, T; Lafontaine, L; Berger, A; Bruneval, P; Fridman, WH; Becker, C; Pagès, F; Speicher, MR; Trajanoski, Z; Galon, J.
Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer.
Immunity. 2013; 39(4):782-795
Doi: 10.1016/j.immuni.2013.10.003
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- Co-Autor*innen der Med Uni Graz
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Obenauf Anna Christina
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Speicher Michael
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- 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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Animals -
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B-Lymphocytes - immunology
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Carcinoma - genetics
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Cell Movement -
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Chemokine CXCL13 - genetics
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Colorectal Neoplasms - genetics
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Gene Expression Profiling -
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Gene Expression Regulation -
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Humans -
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Immunity, Innate -
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Tumor Microenvironment - immunology