title: The Interplay Between Neutrophils and CD8+T Cells Improves Survival in Human Colorectal Cancer.
abstract: Purpose:Tumor infiltration by different T lymphocyte subsets is known to be associated with favorable prognosis in colorectal cancer. Still debated is the role of innate immune system. We investigated clinical relevance, phenotypes, and functional features of colorectal cancer-infiltrating CD66b+neutrophils and their crosstalk with CD8+T cells.Experimental Design:CD66b+and CD8+cell infiltration was analyzed by IHC on a tissue microarray including >650 evaluable colorectal cancer samples. Phenotypic profiles of tissue-infiltrating and peripheral blood CD66b+cells were evaluated by flow cytometry. CD66b+/CD8+cells crosstalk was investigated byin vitroexperiments.Results:CD66b+cell infiltration in colorectal cancer is significantly associated with increased survival. Interestingly, neutrophils frequently colocalize with CD8+T cells in colorectal cancer. Functional studies indicate that although neutrophils are devoid of direct antitumor potential, coculture with peripheral blood or tumor-associated neutrophils (TAN) enhances CD8+T-cell activation, proliferation, and cytokine release induced by suboptimal concentrations of anti-CD3 mAb. Moreover, under optimal activation conditions, CD8+cell stimulation in the presence of CD66b+cells results in increasing numbers of cells expressing CD45RO/CD62L "central memory" phenotype. Importantly, combined tumor infiltration by CD66b+and CD8+T lymphocytes is associated with significantly better prognosis, as compared with CD8+T-cell infiltration alone.Conclusions:Neutrophils enhance the responsiveness of CD8+T cells to T-cell receptor triggering. Accordingly, infiltration by neutrophils enhances the prognostic significance of colorectal cancer infiltration by CD8+T cells, suggesting that they might effectively promote antitumor immunity.Clin Cancer Res; 23(14); 3847-58. ©2017 AACR.
authors.affiliation: Department of Biomedicine, Basel University Hospital and University of Basel, Basel, Switzerland.|Molecular Pathology Division, Institute of Pathology, Basel University Hospital and University of Basel, Switzerland.
authors.forename: Valeria
authors.initials: V
authors.lastname: Governa
authors.affiliation: Department of Biomedicine, Basel University Hospital and University of Basel, Basel, Switzerland.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Trella
authors.affiliation: Department of Biomedicine, Basel University Hospital and University of Basel, Basel, Switzerland.
authors.forename: Valentina
authors.initials: V
authors.lastname: Mele
authors.affiliation: Molecular Pathology Division, Institute of Pathology, Basel University Hospital and University of Basel, Switzerland.
authors.forename: Luigi
authors.initials: L
authors.lastname: Tornillo
authors.affiliation: Department of Biomedicine, Basel University Hospital and University of Basel, Basel, Switzerland.
authors.forename: Francesca
authors.initials: F
authors.lastname: Amicarella
authors.affiliation: Department of Biomedicine, Basel University Hospital and University of Basel, Basel, Switzerland.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Cremonesi
authors.affiliation: Department of Biomedicine, Basel University Hospital and University of Basel, Basel, Switzerland.
authors.forename: Manuele Giuseppe
authors.initials: MG
authors.lastname: Muraro
authors.affiliation: Department of Biomedicine, Basel University Hospital and University of Basel, Basel, Switzerland.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Biomedicine, Basel University Hospital and University of Basel, Basel, Switzerland.|Department of General Surgery, Basel University Hospital and University of Basel, Switzerland.
authors.forename: Raoul
authors.initials: R
authors.lastname: Droeser
authors.affiliation: Department of Biomedicine, Basel University Hospital and University of Basel, Basel, Switzerland.|Department of General Surgery, Basel University Hospital and University of Basel, Switzerland.
authors.forename: Silvio R
authors.initials: SR
authors.lastname: Däster
authors.affiliation: Department of Visceral Surgery, St. Claraspital, Basel, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Bolli
authors.affiliation: Department of Visceral Surgery, Ospedale Civico, Lugano, Switzerland.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Rosso
authors.affiliation: Department of General Surgery, Basel University Hospital and University of Basel, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Oertli
authors.affiliation: Molecular Pathology Division, Institute of Pathology, Basel University Hospital and University of Basel, Switzerland.
authors.forename: Serenella
authors.initials: S
authors.lastname: Eppenberger-Castori
authors.affiliation: Molecular Pathology Division, Institute of Pathology, Basel University Hospital and University of Basel, Switzerland.
authors.forename: Luigi M
authors.initials: LM
authors.lastname: Terracciano
authors.affiliation: Department of Biomedicine, Basel University Hospital and University of Basel, Basel, Switzerland.
authors.forename: Giandomenica
authors.initials: G
authors.lastname: Iezzi
authors.affiliation: Department of Biomedicine, Basel University Hospital and University of Basel, Basel, Switzerland. giulio.spagnoli@usb.ch.
authors.forename: Giulio C
authors.initials: GC
authors.lastname: Spagnoli
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000473:pathology; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D011379:Prognosis; D016176:T-Lymphocyte Subsets / Q000276:immunology; D046888:Tissue Array Analysis
chemical_list: D015703:Antigens, CD; C504120:CEACAM8 protein, human; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins