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

Autor: Gabriela Bindea, Christoph Becker, Wolf H. Fridman, Helen K. Angell, Franck Pagès, Patrick Bruneval, Jérôme Galon, Zlatko Trajanoski, Michael R. Speicher, Tessa Fredriksen, Amos Kirilovsky, Maximilian J. Waldner, Marie Tosolini, Lucie Lafontaine, Anna C. Obenauf, Bernhard Mlecnik, Anne Berger
Rok vydání: 2013
Předmět:
Cell type
Chemokine
Colorectal cancer
animal diseases
Immunology
chemical and pharmacologic phenomena
Article
03 medical and health sciences
Mice
0302 clinical medicine
Immune system
Immunity
Cell Movement
medicine
Tumor Microenvironment
Animals
Humans
Immunology and Allergy
Lymphocyte Count
CXCL13
B cell
030304 developmental biology
Neoplasm Staging
0303 health sciences
B-Lymphocytes
biology
Protein Stability
Gene Expression Profiling
Interleukins
Carcinoma
T-Lymphocytes
Helper-Inducer
biochemical phenomena
metabolism
and nutrition
medicine.disease
Chemokine CXCL13
Survival Analysis
Immunity
Innate
3. Good health
medicine.anatomical_structure
Infectious Diseases
Gene Expression Regulation
Tumor progression
030220 oncology & carcinogenesis
biology.protein
bacteria
Neoplasm Recurrence
Local
Colorectal Neoplasms
Zdroj: Immunity; Vol 39
ISSN: 1074-7613
DOI: 10.1016/j.immuni.2013.10.003
Popis: SummaryThe 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.
Databáze: OpenAIRE
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