title: Negative prognostic impact of regulatory T cell infiltration in surgically resected esophageal cancer post-radiochemotherapy.
abstract: Ever accumulating evidence indicates that the long-term effects of radiotherapy and chemotherapy largely depend on the induction (or restoration) of an anticancer immune response. Here, we investigated this paradigm in the context of esophageal carcinomas treated by neo-adjuvant radiochemotherapy, in a cohort encompassing 196 patients. We found that the density of the FOXP3+ regulatory T cell (Treg) infiltrate present in the residual tumor (or its scar) correlated with the pathological response (the less Tregs the more pronounced was the histological response) and predicted cancer-specific survival. In contrast, there was no significant clinical impact of the frequency of CD8+ cytotoxic T cells. At difference with breast or colorectal cancer, a loss-of-function allele of toll like receptor 4 (TLR4) improved cancer-specific survival of patients with esophageal cancer. While a loss-of-function allele of purinergic receptor P2X, ligand-gated ion channel, 7 (P2RX7) failed to affect cancer-specific survival, its presence did correlate with an increase in Treg infiltration. Altogether, these results corroborate the notion that the immunosurveillance seals the fate of patients with esophageal carcinomas treated with conventional radiochemotherapy.
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France.|INSERM, U1138, Paris, France.|Equipe 11 Labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers; Paris, France.|Université Paris Descartes/Paris V,Sorbonne Paris Cité, Paris, France.|Université Pierre et Marie Curie/Paris VI, Paris, France.
authors.forename: Erika
authors.initials: E
authors.lastname: Vacchelli
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France.|INSERM, U1015, Villejuif, France.|Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, France.
authors.forename: Michaela
authors.initials: M
authors.lastname: Semeraro
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France.|INSERM, U1138, Paris, France.|Equipe 11 Labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers; Paris, France.|Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: David P
authors.initials: DP
authors.lastname: Enot
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France.|INSERM, U1138, Paris, France.|Equipe 11 Labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers; Paris, France.|Université Paris Descartes/Paris V,Sorbonne Paris Cité, Paris, France.
authors.forename: Kariman
authors.initials: K
authors.lastname: Chaba
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France.|INSERM, U1015, Villejuif, France.|Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, France.
authors.forename: Vichnou
authors.initials: V
authors.lastname: Poirier Colame
authors.affiliation: Department of Pathology, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Peggy
authors.initials: P
authors.lastname: Dartigues
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France.|INSERM, U1015, Villejuif, France.|Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, France.
authors.forename: Aurelie
authors.initials: A
authors.lastname: Perier
authors.affiliation: Digital Pathology, Departement of Pathology, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Irene
authors.initials: I
authors.lastname: Villa
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France.|INSERM, U1015, Villejuif, France.|Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rusakiewicz
authors.affiliation: Department of Digestive and Oncological Surgery, Claude Huriez University Hospital, Lille, France.|North of France University, Lille, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Gronnier
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France.|Department of Surgical Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Diane
authors.initials: D
authors.lastname: Goéré
authors.affiliation: Department of Digestive and Oncological Surgery, Claude Huriez University Hospital, Lille, France.|North of France University, Lille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Mariette
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France.|INSERM, U1015, Villejuif, France.|Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, France.|Faculté de Médecine, Université Paris-Sud/Paris XI, Kremlin-Bicêtre, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France.|INSERM, U1138, Paris, France.|Equipe 11 Labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers; Paris, France.|Université Paris Descartes/Paris V,Sorbonne Paris Cité, Paris, France.|Université Pierre et Marie Curie/Paris VI, Paris, France.|Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France.|Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000483:Alleles; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D059248:Chemoradiotherapy / Q000379:methods*; D015331:Cohort Studies; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000532:radiotherapy; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D011379:Prognosis; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C546468:P2RX7 protein, human; D058486:Receptors, Purinergic P2X7; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4
keywords: ATG16L1; apoptosis; autophagy; immunogenic cell death; pattern recognition receptor