title: Tumor infiltration by Tbet+ effector T cells and CD20+ B cells is associated with survival in gastric cancer patients.
abstract: Tumor-infiltrating T and B lymphocytes could have the potential to affect cancer prognosis. The objective of this study was to investigate the prognostic significance of tumor infiltration by CD8 and CD4 T cells, and B lymphocytes in patients with localized gastric cancer. In a retrospective cohort of 82 patients with localized gastric cancer and treated by surgery we quantitatively assessed by immunohistochemistry on surgical specimen, immune infiltrates of IL-17+, CD8+, Foxp3+, Tbet+T cells and CD20+B cells both in the tumor core and at the invasive margin via immunohistochemical analyses of surgical specimens. We observed that CD8+and IL17+T-cell densities were not significantly associated with gastric cancer prognosis. In contrast, high infiltration of Tbet+T cells, high numbers of CD20+B-cell follicles, and low infiltration of Foxp3+T cells, were associated with better relapse-free survival. Interestingly, treatment with neoadjuvant chemotherapy or histological tumor type (diffuse versus intestinal) did not influence type and density of immune infiltrates or their prognostic value. Immunohistochemical analysis of the gastric cancer stromal microenvironment revealed organized T and B cell aggregates, with strong structural analogies to normal secondary lymphoid organs and which could be considered as tertiary lymphoid structures. Using transcriptomic data from an independent cohort of 365 localized gastric cancer, we confirmed that a coordinated Th1, and B cell stromal gene signature is associated with better outcome. Altogether, these data suggest that tumor infiltration by B and Th1 T cells could affect gastric cancer prognosis and may be used to better define the outcome of patients with localized gastric cancer.
authors.affiliation: Department of Medical Oncology Center Georges François Leclerc; Dijon, France; Faculté des Sciences de Santé; Université de Bourgogne; Dijon, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Hennequin
authors.affiliation: Faculté des Sciences de Santé; Université de Bourgogne; Dijon, France; Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 866; Dijon, France; Department of Biology and Pathology of Tumors. Plateform of Genetic; Immunology and Histology of Solid Tumors; Centre Georges-François Leclerc; Dijon, France.
authors.forename: Valentin
authors.initials: V
authors.lastname: Derangère
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 866; Dijon, France; Department of Biology and Pathology of Tumors. Plateform of Genetic; Immunology and Histology of Solid Tumors; Centre Georges-François Leclerc; Dijon, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Boidot
authors.affiliation: Department of Medical Oncology Center Georges François Leclerc; Dijon, France; Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 866; Dijon, France; Department of Biology and Pathology of Tumors. Plateform of Genetic; Immunology and Histology of Solid Tumors; Centre Georges-François Leclerc; Dijon, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Apetoh
authors.affiliation: Department of Medical Oncology Center Georges François Leclerc ; Dijon, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Vincent
authors.affiliation: Department of Surgical Oncology. Center Georges François Leclerc ; Dijon, France.
authors.forename: David
authors.initials: D
authors.lastname: Orry
authors.affiliation: Department of Surgical Oncology. Center Georges François Leclerc ; Dijon, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Fraisse
authors.affiliation: Department of Surgical Oncology. Center Georges François Leclerc ; Dijon, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Causeret
authors.affiliation: Faculté des Sciences de Santé; Université de Bourgogne; Dijon, France; Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 866; Dijon, France.
authors.forename: François
authors.initials: F
authors.lastname: Martin
authors.affiliation: Department of Biology and Pathology of Tumors. Plateform of Genetic; Immunology and Histology of Solid Tumors; Centre Georges-François Leclerc ; Dijon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Arnould
authors.affiliation: Department of Biology and Pathology of Tumors. Plateform of Genetic; Immunology and Histology of Solid Tumors; Centre Georges-François Leclerc ; Dijon, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Beltjens
authors.affiliation: Department of Medical Oncology Center Georges François Leclerc; Dijon, France; Faculté des Sciences de Santé; Université de Bourgogne; Dijon, France; Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 866; Dijon, France; Department of Biology and Pathology of Tumors. Plateform of Genetic; Immunology and Histology of Solid Tumors; Centre Georges-François Leclerc; Dijon, France.
authors.forename: François
authors.initials: F
authors.lastname: Ghiringhelli
authors.affiliation: Department of Medical Oncology Center Georges François Leclerc; Dijon, France; Faculté des Sciences de Santé; Université de Bourgogne; Dijon, France; Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 866; Dijon, France; Department of Biology and Pathology of Tumors. Plateform of Genetic; Immunology and Histology of Solid Tumors; Centre Georges-François Leclerc; Dijon, France; Faculté des Sciences de Santé; Université de Bourgogne; Dijon, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Ladoire
keywords: B cells; T-bet; gastric cancer; histology; human tumors; prognosis