Negative prognostic impact of regulatory T cell infiltration in surgically resected esophageal cancer post-radiochemotherapy

// Erika Vacchelli 1,2,3,4,5 , Michaela Semeraro 1,6,7 , David P. Enot 1,2,3,8 , Kariman Chaba 1,2,3,4 , Vichnou Poirier Colame 1,6,7 , Peggy Dartigues 9 , Aurelie Perier 1,6,7 , Irene Villa 10 , Sylvie Rusakiewicz 1,6,7 , Caroline Gronnier 11,12 , Diane Goéré 1,13 , Christophe Mariette 11,12 , Laurence Zitvogel 1,6,7,14,* and Guido Kroemer 1,2,3,4,5,8,15,* 1 Gustave Roussy Cancer Campus, Villejuif, France 2 INSERM, U1138, Paris, France 3 Equipe 11 Labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France 4 Université Paris Descartes/Paris V,Sorbonne Paris Cité, Paris, France 5 Université Pierre et Marie Curie/Paris VI, Paris, France 6 INSERM, U1015, Villejuif, France 7 Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, France 8 Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France 9 Department of Pathology, Gustave Roussy Cancer Campus, Villejuif, France 10 Digital Pathology, Departement of Pathology, Gustave Roussy Cancer Campus, Villejuif, France 11 Department of Digestive and Oncological Surgery, Claude Huriez University Hospital, Lille, France 12 North of France University, Lille, France 13 Department of Surgical Oncology, Gustave Roussy Cancer Campus, Villejuif, France 14 Faculté de Médecine, Université Paris-Sud/Paris XI: Kremlin-Bicêtre, France 15 Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France * share senior co-authorship Correspondence to: Guido Kroemer, email: // Laurence Zitvogel, email: // Keywords : immunogenic cell death, autophagy, ATG16L1, pattern recognition receptor, apoptosis Received : May 05, 2015 Accepted : June 05, 2015 Published : June 10, 2015 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.