title: Tumor-infiltrating T lymphocytes improve clinical outcome of therapy-resistant neuroblastoma.
abstract: Neuroblastoma grows within an intricate network of different cell types including epithelial, stromal and immune cells. The presence of tumor-infiltrating T cells is considered an important prognostic indicator in many cancers, but the role of these cells in neuroblastoma remains to be elucidated. Herein, we examined the relationship between the type, density and organization of infiltrating T cells and clinical outcome within a large collection of neuroblastoma samples by quantitative analysis of immunohistochemical staining. We found that infiltrating T cells have a prognostic value greater than, and independent of, the criteria currently used to stage neuroblastoma. A variablein situstructural organization and different concurrent infiltration of T-cell subsets were detected in tumors with various outcomes. Low-risk neuroblastomas were characterized by a higher number of proliferating T cells and a more structured T-cell organization, which was gradually lost in tumors with poor prognosis. We defined an immunoscore based on the presence of CD3+, CD4+and CD8+infiltrating T cells that associates with favorable clinical outcome in MYCN-amplified tumors, improving patient survival when combined with the v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) status. These findings support the hypothesis that infiltrating T cells influence the behavior of neuroblastoma and might be of clinical importance for the treatment of patients.
authors.affiliation: Fondazione Bruno Kessler ; Povo, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Mina
authors.affiliation: Paediatric Haematology/Oncology Department; IRCCS; Ospedale Pediatrico Bambino Gesù , Rome, Italy.
authors.forename: Renata
authors.initials: R
authors.lastname: Boldrini
authors.affiliation: Paediatric Haematology/Oncology Department; IRCCS; Ospedale Pediatrico Bambino Gesù , Rome, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Citti
authors.affiliation: Paediatric Haematology/Oncology Department; IRCCS; Ospedale Pediatrico Bambino Gesù , Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Romania
authors.affiliation: Paediatric Haematology/Oncology Department; IRCCS; Ospedale Pediatrico Bambino Gesù , Rome, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: D'Alicandro
authors.affiliation: Paediatric Haematology/Oncology Department; IRCCS; Ospedale Pediatrico Bambino Gesù , Rome, Italy.
authors.forename: Maretta
authors.initials: M
authors.lastname: De Ioris
authors.affiliation: Paediatric Haematology/Oncology Department; IRCCS; Ospedale Pediatrico Bambino Gesù , Rome, Italy.
authors.forename: Aurora
authors.initials: A
authors.lastname: Castellano
authors.affiliation: Fondazione Bruno Kessler ; Povo, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Furlanello
authors.affiliation: Paediatric Haematology/Oncology Department; IRCCS; Ospedale Pediatrico Bambino Gesù , Rome, Italy ; University of Pavia ; Pavia, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.affiliation: Paediatric Haematology/Oncology Department; IRCCS; Ospedale Pediatrico Bambino Gesù , Rome, Italy.
authors.forename: Doriana
authors.initials: D
authors.lastname: Fruci
keywords: T cells; clinical outcome; correlation network analysis; neuroblastoma; prognostic marker; tumor-infiltrating T lymphocytes