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ResearchIn-Press PreviewImmunologyOncology Open Access | 10.1172/JCI166085
1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
Find articles by Domblides, C. in: JCI | PubMed | Google Scholar |
1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
Find articles by Crampton, S. in: JCI | PubMed | Google Scholar
1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
Find articles by Liu, H. in: JCI | PubMed | Google Scholar
1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
Find articles by Bartleson, J. in: JCI | PubMed | Google Scholar |
1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
Find articles by Nguyen, A. in: JCI | PubMed | Google Scholar
1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
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1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
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1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
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1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
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1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
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1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
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1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
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1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
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1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
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1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
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1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
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1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
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1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
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1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
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1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
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1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
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1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
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1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
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1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
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1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
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1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
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1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
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1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
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1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
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1University of Bordeaux, Bordeaux, France
2Immunology Discovery, Janssen Research and Development, San Diego, United States of America
3Takeda Pharmaceuticals, Cambridge, United States of America
4Buck Institute for Research on Aging, Novato, United States of America
5Department of Medicine, McGill University, Montreal, Canada
6Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
7Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, United States of America
8INSERM, U1218 ACTION, Bordeaux, France
9ImmunoConcEpt, University of Bordeaux, Bordeaux, France
10Department of Biopathology, Institut Bergonié, Bordeaux, France
11QuantaCell, Montpellier, France
12INRS Santé Biotechnologie, Laval, Canada
13Pediatric Rheumatology, Children's Hospital of Philadelphia, Philadelphia, United States of America
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Published April 23, 2024 - More info
The immune system can control cancer progression. However, even though some innate immune sensors of cellular stress are expressed intrinsically in epithelial cells, their potential role in cancer aggressiveness and subsequent overall survival in humans is mainly unknown. Here, we show that NLR family CARD Domain Containing 4 (NLRC4) is downregulated in epithelial tumor cells of colorectal cancer (CRC) patients by using spatial tissue imaging. Strikingly, only the loss of tumor NLRC4 but not stromal is associated with poor immune infiltration (mainly dendritic and CD4+/CD8+ T cells) and accurately predicts progression to metastatic Stage IV and decrease of overall survival. By combining multi-omics approaches, we show that restoring NLRC4 expression in human colorectal cancer cells triggers a broad inflammasome-independent immune reprogramming consisting of Type-I IFN signaling genes and the release of chemokines and myeloid growth factors involved in the tumor infiltration and activation of dendritic cells (DCs) and T cells. Consistently, such reprogramming in cancer cells is sufficient to directly mature human DCs towards a Th1 antitumor immune response through IL-12 production in vitro. In multiple human carcinomas (colorectal, lung, and skin), we confirmed that NLRC4 expression in patient tumors is strongly associated with Type-I IFN genes, immune infiltrates and high microsatellite instability. Thus, we shed light on the epithelial innate immune sensor NLRC4 as a novel therapeutic target to promote an efficient antitumor immune response against the aggressiveness of various carcinomas.