title: Peripheral ENO1-specific T cells mirror the intratumoral immune response and their presence is a potential prognostic factor for pancreatic adenocarcinoma.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with an average survival of 4-6 months following diagnosis. Surgical resection is the only treatment with curative intent, but resectable PDAC patients are in the minority. Also, unlike other neoplasms, PDAC is resistant to conventional and targeted chemotherapy. Innovative treatments, such as immunotherapy, can be very important and the study of the immune response is fundamental. We previously demonstrated that PDAC patients show tumor-infiltrating T cells specific to α-enolase (ENO1), a glycolytic enzyme over-expressed by pancreatic tumor cells, which plays an important role in promoting cell migration and cancer metastasis. In the present study, we evaluate the functional anticancer proprieties of ENO1-specific T cells isolated from the peripheral blood of PDAC patients. Furthermore, comparing the T cell receptor repertoire of ENO1-specific peripheral and infiltrating tumor T cells from the same patient suggests that ENO1-specific T cells, despite having a different functional profile, can recirculate from the tumor to the periphery. Finally, of clinical relevance, the presence of peripheral ENO1-specific T cells has a prognostic value and significantly correlates with a longer survival.
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, and Department of Biomedicine, Azienda Ospedaliera Universitaria Careggi (AOUC), I-50134 Florence, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Niccolai
authors.affiliation: Centre for Experimental Research and Medical Studies (CERMS), AOU City of Health and Science of Turin, and Department of Molecular Biotechnology and Health Sciences, University of Turin, I-10126 Turin, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Cappello
authors.affiliation: Department of Surgery and Translational Medicine, University of Florence, and Department of Biomedicine, Azienda Ospedaliera Universitaria Careggi (AOUC), I-50134 Florence, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Taddei
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, and Department of Biomedicine, Azienda Ospedaliera Universitaria Careggi (AOUC), I-50134 Florence, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Ricci
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, and Department of Biomedicine, Azienda Ospedaliera Universitaria Careggi (AOUC), I-50134 Florence, Italy.
authors.forename: Mario Milco
authors.initials: MM
authors.lastname: D'Elios
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, and Department of Biomedicine, Azienda Ospedaliera Universitaria Careggi (AOUC), I-50134 Florence, Italy.
authors.forename: Marisa
authors.initials: M
authors.lastname: Benagiano
authors.affiliation: Department of Surgery and Translational Medicine, University of Florence, and Department of Biomedicine, Azienda Ospedaliera Universitaria Careggi (AOUC), I-50134 Florence, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bechi
authors.affiliation: Division of General and Oncologic Surgery, Department of Oncology, Azienda Ospedaliera Universitaria Careggi (AOUC), I-50134 Florence, Italy.
authors.forename: Lapo
authors.initials: L
authors.lastname: Bencini
authors.affiliation: Department of Surgery and Translational Medicine, University of Florence, and Department of Biomedicine, Azienda Ospedaliera Universitaria Careggi (AOUC), I-50134 Florence, Italy.
authors.forename: Maria Novella
authors.initials: MN
authors.lastname: Ringressi
authors.affiliation: Division of General and Oncologic Surgery, Department of Oncology, Azienda Ospedaliera Universitaria Careggi (AOUC), I-50134 Florence, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Coratti
authors.affiliation: Department of Surgery and Translational Medicine, University of Florence, and Department of Biomedicine, Azienda Ospedaliera Universitaria Careggi (AOUC), I-50134 Florence, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Cianchi
authors.affiliation: Centre for Experimental Research and Medical Studies (CERMS), AOU City of Health and Science of Turin, and Department of Molecular Biotechnology and Health Sciences, University of Turin, I-10126 Turin, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Bonello
authors.affiliation: General Anatomopathology and Molecular Oncogenetics - AOU City of Health and Science of Turin, I-10126 Turin, Italy.
authors.forename: Paola Francia
authors.initials: PF
authors.lastname: Di Celle
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, and Department of Biomedicine, Azienda Ospedaliera Universitaria Careggi (AOUC), I-50134 Florence, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Prisco
authors.affiliation: Centre for Experimental Research and Medical Studies (CERMS), AOU City of Health and Science of Turin, and Department of Molecular Biotechnology and Health Sciences, University of Turin, I-10126 Turin, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Novelli
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, and Department of Biomedicine, Azienda Ospedaliera Universitaria Careggi (AOUC), I-50134 Florence, Italy.
authors.forename: Amedeo
authors.initials: A
authors.lastname: Amedei
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000097:blood*; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000097:blood*; D011379:Prognosis; D011948:Receptors, Antigen, T-Cell / Q000097:blood*; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology; D025521:Tumor Suppressor Proteins / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D011948:Receptors, Antigen, T-Cell; D025521:Tumor Suppressor Proteins; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase