title: The ratio of CD8+/FOXP3 T lymphocytes infiltrating breast tissues predicts the relapse of ductal carcinomain situ.
abstract: In a series of 248 tumor samples obtained from image-guided biopsies from patients diagnosed with ductal carcinomain situof the breast, we attempted to identify biomarkers that predict microinfiltration at definitive surgery or relapse during follow-up. For this, we used immunohistochemical methods, followed by automated image analyses, to measure the mean diameter of nuclei (which correlates with ploidy), the phosphorylation of eukaryotic initiation factor 2α (eIF2α, which reflects endoplasmic reticulum stress) as well as the density and ratio of CD8+cytotoxic T lymphocytes and FOXP3+regulatory T cells. The median nuclear diameter of malignant cells correlated with eIF2α phosphorylation (in cancerous tissue), which in turn correlated with the density of the CD8+infiltrate and the CD8+/FOXP3 ratio (both in cancerous and the adjacent non-cancerous parenchyma). Neither microinfiltration nor lymph node involvement was associated with the probability of relapse. Both correlated positively with the CD8+/FOXP3 ratio in the malignant area. In contrast, relapse was associated with a paucity of the CD8+infiltrate as well as an unfavorable CD8+/FOXP3 ratio, both in malignant and non-malignant parenchyma. The combined analysis of the CD8+/FOXP3 ratio in cancerous and non-cancerous tissues revealed a significant impact of their interaction on the probability of relapse, but not on the presence of microinfiltration or lymph node metastasis. Altogether, these results support the idea of an immunosurveillance system that determines the risk of relapse in ductal carcinomain situof the breast.
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France; INSERM, U1138, Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Center de Recherche des Cordeliers, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Université Pierre et Marie Curie, Paris, France.
authors.forename: Michaela
authors.initials: M
authors.lastname: Semeraro
authors.affiliation: Department of Medical Biology and Pathology, Gustave Roussy Cancer Campus, Villejuif, France; Module de Développement en Pathologie Expérimentale-INSERM U981, Gustave-Roussy Cancer Campus, Villejuif, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Adam
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France; INSERM, U1138, Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Center de Recherche des Cordeliers, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Université Pierre et Marie Curie, Paris, France.
authors.forename: Gautier
authors.initials: G
authors.lastname: Stoll
authors.affiliation: Module de Développement en Pathologie Expérimentale-INSERM U981, Gustave-Roussy Cancer Campus , Villejuif, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Louvet
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France; INSERM, U1138, Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Center de Recherche des Cordeliers, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Université Pierre et Marie Curie, Paris, France.
authors.forename: Kariman
authors.initials: K
authors.lastname: Chaba
authors.affiliation: Faculté de Médecine, Université Paris-Saclay, Kremlin-Bicêtre, France; Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 507, Villejuif, France; Department of Immuno-Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Vichnou
authors.initials: V
authors.lastname: Poirier-Colame
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France; INSERM, U1138, Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Center de Recherche des Cordeliers, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Université Pierre et Marie Curie, Paris, France.
authors.forename: Allan
authors.initials: A
authors.lastname: Sauvat
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France; INSERM, U1138, Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Center de Recherche des Cordeliers, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Université Pierre et Marie Curie, Paris, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Senovilla
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France; INSERM, U1138, Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Center de Recherche des Cordeliers, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Université Pierre et Marie Curie, Paris, France.
authors.forename: Erika
authors.initials: E
authors.lastname: Vacchelli
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France; INSERM, U1138, Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Center de Recherche des Cordeliers, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Université Pierre et Marie Curie, Paris, France; Faculté de Médecine, Université Paris-Saclay, Kremlin-Bicêtre, France.
authors.forename: Norma
authors.initials: N
authors.lastname: Bloy
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France; INSERM, U1138, Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Center de Recherche des Cordeliers, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Université Pierre et Marie Curie, Paris, France; Faculté de Médecine, Université Paris-Saclay, Kremlin-Bicêtre, France.
authors.forename: Juliette
authors.initials: J
authors.lastname: Humeau
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France; INSERM, U1138, Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Center de Recherche des Cordeliers, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Université Pierre et Marie Curie, Paris, France.
authors.forename: Aitziber
authors.initials: A
authors.lastname: Buque
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France; INSERM, U1138, Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Center de Recherche des Cordeliers, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Université Pierre et Marie Curie, Paris, France.
authors.forename: Oliver
authors.initials: O
authors.lastname: Kepp
authors.affiliation: Faculté de Médecine, Université Paris-Saclay, Kremlin-Bicêtre, France; Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 507, Villejuif, France; Department of Immuno-Oncology, Gustave Roussy Cancer Campus, Villejuif, France; INSERM, U1015, Villejuif, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.affiliation: INSERM, U981 "Identification of molecular predictors and new targets for cancer treatment", Villejuif, France; Department of Medical Oncology and Breast Cancer Group, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: André
authors.affiliation: Department of Medical Biology and Pathology, Gustave Roussy Cancer Campus , Villejuif, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Mathieu
authors.affiliation: Department of Medical Oncology and Breast Cancer Group, Gustave Roussy Cancer Campus , Villejuif, France.
authors.forename: Suzette
authors.initials: S
authors.lastname: Delaloge
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France; INSERM, U1138, Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Center de Recherche des Cordeliers, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Université Pierre et Marie Curie, Paris, France; Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France; Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
keywords: Cytotoxic T cells; hyperploidy; immunogenic cell death; immunosuppressive regulatory T cells; intraductal carcinoma