title: Relationship of dendritic cell density, HMGB1 expression, and tumor-infiltrating lymphocytes in non-small cell lung carcinomas.
abstract: Lung cancer is the leading cause of cancer death worldwide and non-small cell lung carcinoma (NSCLC) is the most common type of lung carcinomas. In adenocarcinomas, the most frequent histologic type of NSCLC, dendritic cells (DCs) are localized in close contact with tumor cells, and tumor-infiltrating lymphocytes (TILs) are observed in the peritumoral zones. In NSCLC, no studies investigating the density of intratumoral DCs and their impact on the density of TILs have been performed. In addition, the role of the alarmin high-mobility group box1 (HMGB1) in intratumoral DCs recruitment has not been analyzed. In the present study, a total of 82 cases of advanced stages of NSCLC were included. Tissue samples were obtained from biopsies and autopsies. DCs in biopsies or combinations of DCs and NK cells, CD3 T lymphocytes, or CD8 T lymphocytes from autopsy specimens were quantified in high power fields. Also, distribution of HMGB1 in tumor cells was detected. In lung adenocarcinomas, irrespective of subclassification, high densities of infiltrating DCs directly associated to high densities of peritumoral TILs. A 2.5-fold increase in TILs was found in specimens with high densities of infiltrating DCs compared with TILs from adenocarcinomas with low densities of infiltrating DCs. High densities of infiltrating DCs were associated with lung adenocarcinomas expressing cytoplasmic or nuclear-cytoplasmic HMGB1. Our results suggest that in adenocarcinoma patients, HMGB1 produced by tumor cells recruits DCs, which associate to an increase of TILs. Encouraging tumor-DCs-T lymphocytes interactions should improve the quality of life and survival of NSCLC patients.
authors.affiliation: *Department of Chronic-Degenerative Diseases ‡Department of Pathology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas †Posgrado en Ciencias Biologicas, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico.
authors.forename: Dolores
authors.initials: D
authors.lastname: Aguilar-Cazares
authors.forename: Manuel
authors.initials: M
authors.lastname: Meneses-Flores
authors.forename: Heriberto
authors.initials: H
authors.lastname: Prado-Garcia
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Islas-Vazquez
authors.forename: Veronica
authors.initials: V
authors.lastname: Rojo-Leon
authors.forename: Susana
authors.initials: S
authors.lastname: Romero-Garcia
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Rivera-Rosales
authors.forename: Jose S
authors.initials: JS
authors.lastname: Lopez-Gonzalez
mesh_terms: D001344:Autopsy; D001706:Biopsy; D017252:CD3 Complex / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology*; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000473:pathology*; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology*; D021381:Protein Transport
chemical_list: D017252:CD3 Complex; D024243:HMGB1 Protein