title: Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer.
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.
authors.affiliation: INSERM U872, Laboratory of Integrative Cancer Immunology, Paris 75006, France; Université Paris Descartes, Paris 75006, France; Cordeliers Research Centre, Université Pierre et Marie Curie Paris 6, Paris 75006, France.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Bindea
authors.forename: Bernhard
authors.initials: B
authors.lastname: Mlecnik
authors.forename: Marie
authors.initials: M
authors.lastname: Tosolini
authors.forename: Amos
authors.initials: A
authors.lastname: Kirilovsky
authors.forename: Maximilian
authors.initials: M
authors.lastname: Waldner
authors.forename: Anna C
authors.initials: AC
authors.lastname: Obenauf
authors.forename: Helen
authors.initials: H
authors.lastname: Angell
authors.forename: Tessa
authors.initials: T
authors.lastname: Fredriksen
authors.forename: Lucie
authors.initials: L
authors.lastname: Lafontaine
authors.forename: Anne
authors.initials: A
authors.lastname: Berger
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruneval
authors.forename: Wolf Herman
authors.initials: WH
authors.lastname: Fridman
authors.forename: Christoph
authors.initials: C
authors.lastname: Becker
authors.forename: Franck
authors.initials: F
authors.lastname: Pagès
authors.forename: Michael R
authors.initials: MR
authors.lastname: Speicher
authors.forename: Zlatko
authors.initials: Z
authors.lastname: Trajanoski
authors.forename: Jérôme
authors.initials: J
authors.lastname: Galon
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002277:Carcinoma / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D002465:Cell Movement; D054382:Chemokine CXCL13 / Q000235:genetics / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D018655:Lymphocyte Count; D051379:Mice; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D055550:Protein Stability; D016019:Survival Analysis; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000473:pathology; D059016:Tumor Microenvironment / Q000276:immunology; D000098546:Interleukin-21
chemical_list: C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; D007378:Interleukins; D000098546:Interleukin-21