PDAC (pancreatic ductal adenocarcinoma) is the fifth leading cause of cancer-related death. The causes of this cancer remain unknown, but increasing evidence indicates a key role of the host immune response and cytokines in human carcinogenesis. Intra-tumoral IL (interleukin)-22 levels have been shown to be elevated in PDAC patients. However, little is known regarding the expression and clinical relevance of Th22 cells in human PDAC and, furthermore, which TILs (tumour-infiltrating lymphocytes) are the main producers of IL-22 is unknown. In the present study, we characterized the functional proprieties of the different subsets of IL-22-producing TILs and analysed their relationship with the TNM staging system and patient survival. We have demonstrated for the first time that, in PDAC patients, the T-cells co-producing IFN-γ (interferon γ) and exerting perforin-mediated cytotoxicity are the major intra-tumoral source of IL-22. In addition, isolated Th22 cells were able to induce apoptosis, which was antagonized by IL-22. Finally, we observed that the IL-22-producing T-cells were significantly increased in tumour tissue and that this increase was positively correlated with TNM staging of PDAC and poorer patient survival. These novel findings support the dual role of the anti-tumour immune system and that IL-22-producing cells may participate in PDAC pathogenesis. Therefore monitoring Th22 levels could be a good diagnostic parameter, and blocking IL-22 signalling may represent a viable method for anti-PDAC therapies.
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February 2016
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Image modified from a figure representing the 5 mechanisms of annexin A1 externalization through non-classic secretory pathways, discussed by Boudhraa et al in issue 130(4) of Clinical Science. For further details please see pp. 205–220. Image kindly provided by Z. Boudhraa, B. Bouchon, C. Viallard, M. D'Incan and F. Degoul.
Research Article|
January 14 2016
Intra-tumoral IFN-γ-producing Th22 cells correlate with TNM staging and the worst outcomes in pancreatic cancer
Elena Niccolai;
Elena Niccolai
*Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy
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Antonio Taddei;
Antonio Taddei
†Immunogenetics and Transplant Biology Service, Azienda Ospedaliera Città della Salute e della Scienza di Torino, via Santena 19, 10126 Turin, Italy
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Federica Ricci;
Federica Ricci
*Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy
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Simona Rolla;
Simona Rolla
‡Centre for Experimental Research and Medical Studies (CERMS), Azienda Ospedaliera Città della Salute e della Scienza di Torino, via Cherasco 15, 10126 Turin, Italy
§Molecular Biology Center and Department of Molecular Biotechnology and Health Sciences, University of Turin, via Nizza 52, 10126 Turin, Italy
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Mario Milco D'Elios;
Mario Milco D'Elios
*Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy
║Department of Neuro-Skeletal Muscle and Sensory Organs, Interdisciplinary Internal Medicine Unit, Azienda Ospedaliero Universitaria Careggi, 50134 Florence, Italy
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Marisa Benagiano;
Marisa Benagiano
*Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy
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Paolo Bechi;
Paolo Bechi
¶Department of Surgery and Translational Medicine, University of Florence, Viale Michelangiolo 41, 50125 Florence, Italy
**Department of Biomedicine, Azienda Ospedaliera Universitaria Careggi (AOUC), Largo Brambilla 3, 50134 Florence, Italy
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Lapo Bencini;
Lapo Bencini
††Department of Oncology, Division of General and Oncologic Surgery, Azienda Ospedaliera Universitaria Careggi (AOUC), Largo Brambilla 3, 50134 Florence, Italy
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Maria Novella Ringressi;
Maria Novella Ringressi
¶Department of Surgery and Translational Medicine, University of Florence, Viale Michelangiolo 41, 50125 Florence, Italy
**Department of Biomedicine, Azienda Ospedaliera Universitaria Careggi (AOUC), Largo Brambilla 3, 50134 Florence, Italy
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Alessandro Pini;
Alessandro Pini
*Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy
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Francesca Castiglione;
Francesca Castiglione
*Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy
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Daniele Giordano;
Daniele Giordano
‡Centre for Experimental Research and Medical Studies (CERMS), Azienda Ospedaliera Città della Salute e della Scienza di Torino, via Cherasco 15, 10126 Turin, Italy
§Molecular Biology Center and Department of Molecular Biotechnology and Health Sciences, University of Turin, via Nizza 52, 10126 Turin, Italy
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Maria Antonietta Satolli;
Maria Antonietta Satolli
‡‡Centro Oncologico Ematologico Subalpino (COES), AOU Città della Salute e della Scienza di Torino, 10126 Turin, Italy
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Andrea Coratti;
Andrea Coratti
††Department of Oncology, Division of General and Oncologic Surgery, Azienda Ospedaliera Universitaria Careggi (AOUC), Largo Brambilla 3, 50134 Florence, Italy
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Fabio Cianchi;
Fabio Cianchi
¶Department of Surgery and Translational Medicine, University of Florence, Viale Michelangiolo 41, 50125 Florence, Italy
**Department of Biomedicine, Azienda Ospedaliera Universitaria Careggi (AOUC), Largo Brambilla 3, 50134 Florence, Italy
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Daniele Bani;
Daniele Bani
*Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy
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Domenico Prisco;
Domenico Prisco
*Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy
║Department of Neuro-Skeletal Muscle and Sensory Organs, Interdisciplinary Internal Medicine Unit, Azienda Ospedaliero Universitaria Careggi, 50134 Florence, Italy
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Francesco Novelli;
†Immunogenetics and Transplant Biology Service, Azienda Ospedaliera Città della Salute e della Scienza di Torino, via Santena 19, 10126 Turin, Italy
‡Centre for Experimental Research and Medical Studies (CERMS), Azienda Ospedaliera Città della Salute e della Scienza di Torino, via Cherasco 15, 10126 Turin, Italy
§Molecular Biology Center and Department of Molecular Biotechnology and Health Sciences, University of Turin, via Nizza 52, 10126 Turin, Italy
Correspondence: Professor Amedeo Amedei (email [email protected]) or Professor Francesco Novelli (email [email protected]).
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Amedeo Amedei
*Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy
║Department of Neuro-Skeletal Muscle and Sensory Organs, Interdisciplinary Internal Medicine Unit, Azienda Ospedaliero Universitaria Careggi, 50134 Florence, Italy
Correspondence: Professor Amedeo Amedei (email [email protected]) or Professor Francesco Novelli (email [email protected]).
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Publisher: Portland Press Ltd
Received:
June 19 2015
Revision Received:
November 16 2015
Accepted:
November 20 2015
Accepted Manuscript online:
November 20 2015
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 Authors; published by Portland Press Limited
2016
Clin Sci (Lond) (2016) 130 (4): 247–258.
Article history
Received:
June 19 2015
Revision Received:
November 16 2015
Accepted:
November 20 2015
Accepted Manuscript online:
November 20 2015
Citation
Elena Niccolai, Antonio Taddei, Federica Ricci, Simona Rolla, Mario Milco D'Elios, Marisa Benagiano, Paolo Bechi, Lapo Bencini, Maria Novella Ringressi, Alessandro Pini, Francesca Castiglione, Daniele Giordano, Maria Antonietta Satolli, Andrea Coratti, Fabio Cianchi, Daniele Bani, Domenico Prisco, Francesco Novelli, Amedeo Amedei; Intra-tumoral IFN-γ-producing Th22 cells correlate with TNM staging and the worst outcomes in pancreatic cancer. Clin Sci (Lond) 1 February 2016; 130 (4): 247–258. doi: https://doi.org/10.1042/CS20150437
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