title: Tumor-infiltrating CD14-positive myeloid cells and CD8-positive T-cells prolong survival in patients with cervical carcinoma.
abstract: One of the hallmarks of cancer is the influx of myeloid cells. In our study, we investigated the constitution of tumor-infiltrating myeloid cells and their relationship to other tumor-infiltrating immune cells, tumor characteristics and the disease-specific survival of patients with cervical cancer (CxCa). Triple-color immunofluorescence confocal microscopy was used to locate, identify and quantify macrophages (CD14), their maturation status (CD33) and their polarization (CD163) in a cohort of 86 patients with cervical carcinoma. Quantification of the numbers of myeloid cells revealed that a strong intraepithelial infiltration of CD14+ cells, and more specifically the population of CD14+CD33-CD163- matured M1 macrophages, is associated with a large influx of intraepithelial T lymphocytes (p = 0.008), improved disease-specific survival (p = 0.007) and forms an independent prognostic factor for survival (p = 0.033). The intraepithelial CD8+ T-cell and regulatory T-cell (Treg) ratio also forms an independent prognostic factor (p = 0.010) and combination of these two factors reveals a further increased benefit in survival for patients whose tumor displays a dense infiltration with intraepithelial matured M1 macrophages and a high CD8 T-cell/Treg ratio, indicating that both populations of immune cells simultaneously improve survival. Subsequently, we made a heatmap including all known immune parameters for these patients, whereby we were able to identify different immune signatures in CxCa. These results indicate that reinforcement and activation of the intratumoral M1 macrophages may form an attractive immunotherapeutic option in CxCa.
authors.affiliation: Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: P J
authors.initials: PJ
authors.lastname: de Vos van Steenwijk
authors.forename: T H
authors.initials: TH
authors.lastname: Ramwadhdoebe
authors.forename: R
authors.initials: R
authors.lastname: Goedemans
authors.forename: E M
authors.initials: EM
authors.lastname: Doorduijn
authors.forename: J J
authors.initials: JJ
authors.lastname: van Ham
authors.forename: A
authors.initials: A
authors.lastname: Gorter
authors.forename: T
authors.initials: T
authors.lastname: van Hall
authors.forename: M L
authors.initials: ML
authors.lastname: Kuijjer
authors.forename: M I E
authors.initials: MI
authors.lastname: van Poelgeest
authors.forename: S H
authors.initials: SH
authors.lastname: van der Burg
authors.forename: E S
authors.initials: ES
authors.lastname: Jordanova
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000032:analysis*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology*; D011379:Prognosis; D059016:Tumor Microenvironment; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000401:mortality
chemical_list: D018950:Lipopolysaccharide Receptors
keywords: cervical cancer; myeloid cells; survival; tumor microenvironment