Oncotarget

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

Erika Vacchelli, Michaela Semeraro, David P. Enot, Kariman Chaba, Vichnou Poirier Colame, Peggy Dartigues, Aurelie Perier, Irene Villa, Sylvie Rusakiewicz, Caroline Gronnier, Diane Goéré, Christophe Mariette, Laurence Zitvogel, Guido Kroemer _

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Oncotarget. 2015; 6:20840-20850. https://doi.org/10.18632/oncotarget.4428

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Abstract

Erika Vacchelli1,2,3,4,5, Michaela Semeraro1,6,7, David P. Enot1,2,3,8, Kariman Chaba1,2,3,4, Vichnou Poirier Colame1,6,7, Peggy Dartigues9, Aurelie Perier1,6,7, Irene Villa10, Sylvie Rusakiewicz1,6,7, Caroline Gronnier11,12, Diane Goéré1,13, Christophe Mariette11,12, Laurence Zitvogel1,6,7,14,* and Guido Kroemer1,2,3,4,5,8,15,*

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.


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