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Prognostic Role of Inflammasome Components in Human Colorectal Cancer.
Domblides, Charlotte; Soubeyran, Isabelle; Lartigue, Lydia; Mahouche, Isabelle; Lefort, Félix; Velasco, Valérie; Barnetche, Thomas; Blanco, Patrick; Déchanet-Merville, Julie; Faustin, Benjamin.
Afiliação
  • Domblides C; ImmunoConcEpt Laboratory, CNRS UMR 5164, Bordeaux University, 33076 Bordeaux, France.
  • Soubeyran I; Department of Medical Oncology, Hôpital Saint-André, Bordeaux University Hospital-CHU, 33000 Bordeaux, France.
  • Lartigue L; Comprehensive Cancer Center, Department of Biopathology, Institut Bergonié, 33000 Bordeaux, France.
  • Mahouche I; INSERM, U1218 ACTION, F-33000 Bordeaux, France.
  • Lefort F; INSERM, U1218 ACTION, F-33000 Bordeaux, France.
  • Velasco V; ImmunoConcEpt Laboratory, CNRS UMR 5164, Bordeaux University, 33076 Bordeaux, France.
  • Barnetche T; Comprehensive Cancer Center, Department of Biopathology, Institut Bergonié, 33000 Bordeaux, France.
  • Blanco P; Department of Rheumatology, Bordeaux University Hospital, 33000 Bordeaux, France.
  • Déchanet-Merville J; ImmunoConcEpt Laboratory, CNRS UMR 5164, Bordeaux University, 33076 Bordeaux, France.
  • Faustin B; Department of Immunology and Immunogenetic, FHU ACRONIM, Bordeaux University Hospital, 33000 Bordeaux, France.
Cancers (Basel) ; 12(12)2020 Nov 24.
Article em En | MEDLINE | ID: mdl-33255437
(1) We wanted to assess the prognostic impact of inflammasomes involved in gut epithelial homeostasis and the development of human colorectal cancer (CRC). (2) We investigated the expression of inflammasome components in colonic epithelial cells at the protein level in patient tissues, through an immunofluorescence assay. (3) In a cohort of 104 patients, we found that all inflammasome components were downregulated in CRC. Loss of epithelial (but not stromal) expression of NLRP6, caspase-1 and IL-18 was associated with an increased mortality of 72%, 58% and 68% respectively and to disease progression into metastasis. The loss of epithelial and stromal IL-18 but not NLRP6, was associated to lower tumor immune infiltrates in the lymphoid compartment and higher Programmed cell Death receptor 1 (PD-1) expression. Finally, we found that combined downregulation of IL-18 and NLRP6 was associated with a worse outcome. Indeed, 5-year survival rates were 26% for the NLRP6low/IL-18low tumors, compared to 64.4% for the entire cohort. This downregulation was associated with a more advanced disease (p < 0.0001) and a trend to lower lymphoid cell infiltration. (4) We identified critical inflammasome markers that may help in better stratifying patients for prognosis in CRC and could help clinicians to determine which patients may benefit from immunotherapies.
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Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2020 Tipo de documento: Article