IMMUNOREACT 7: Regular aspirin use is associated with immune surveillance activation in colorectal cancer
Author:
Simoni Ottavia De1, Scarpa Melania1ORCID, Castagliuolo Ignazio2, Stepanyan Astghik2, Angriman Imerio2, Kotsafti Andromachi1, Nacci Camilla2, Scognamiglio Federico2, Negro Silvia2, D’Angelo Antonella2, Chiminazzo Valentina2, Businello Gianluca3, Ruffolo Cesare2, Salmaso Roberta2, Franzato Boris1, Gruppo Mario1, Pilati Pierluigi1, Scapinello Antonio1, Pozza Anna4, Stecca Tommaso4, Massani Marco4, Cataldo Ivana4, Brignola Stefano4, Dei Tos Angelo Paolo2, Ceccon Carlotta2ORCID, Guzzardo Vincenza2, Vignotto Chiara2, Facci Luca2, Maretto Isacco2, Agostini Marco2, Marchegiani Francesco2, Becherucci Giulia5ORCID, Zizzo Maurizio6, Bordignon Giovanni7, Merenda Roberto7, Pirozzolo Giovanni7, Recordare Alfonso7, Pozza Giulia2, Godina Mario7, Mondi Isabella7, Verdi Daunia7, Lio Corrado Da7, Laurino Licia7, Saadeh Luca2, Rivella Giorgio2, Guerriero Silvio8ORCID, Romiti Chiara8, Portale Giuseppe9ORCID, Cipollari Chiara9, Spolverato Ylenia Camilla9, Noaro Giulia9, Cola Roberto9, Candioli Salvatore5, Gavagna Laura5, Ricagna Fabio5, Ortenzi Monica10, Guerrieri Mario10, Tagliente Giovanni11, Tomassi Monica11, Tedeschi Umberto11, Salmaso Beatrice3, Buzzi Gianluca3, Parini Dario3, Prando Daniela3, Zuin Matteo7, Bergamo Francesca1, Zagonel Vittorina1, Porzionato Andrea12, Cavallin Francesco13ORCID, Camillo Barbara Di12, Cristoforo Loretta Di14, Bao Quoc Riccardo2, Pucciarelli Salvatore2ORCID, Bardini Romeo2, Spolverato Gaya2, Fassan Matteo12, Scarpa Marco2ORCID,
Affiliation:
1. Veneto Institute of Oncology IOV‐IRCCS Padova Italy 2. Azienda Ospedale Università di Padova Padova Italy 3. Azienda Unità Socio‐Sanitaria Locale 5 Polesana Rovigo Italy 4. Azienda Unità Socio‐Sanitaria Locale 2 Marca Trevigiana Treviso Italy 5. Azienda Unità Socio‐Sanitaria Locale 1 Dolomiti Belluno Italy 6. Azienda Unità Sanitaria Locale ‐ IRCCS di Reggio Emilia Reggio Emilia Italy 7. Azienda Unità Socio‐Sanitaria Locale 3 Serenissima Venezia Italy 8. Area Vasta 4 di Fermo Ospedale Murri Fermo Italy 9. Azienda Unità Socio‐Sanitaria Locale 6 Euganea Padova Italy 10. Azienda Ospedaliero Universitaria delle Marche Ancona Italy 11. Policlinico di Abano Abano Terme Italy 12. Università degli Studi di Padova Padova Italy 13. Independent Statistician Solagna Italy 14. ASL ROMA 3 Ospedale “Grassi” Ostia Italy
Abstract
AbstractBackgroundLong‐term daily use of aspirin reduces incidence and mortality due to colorectal cancer (CRC). This study aimed to analyze the effect of aspirin on the tumor microenvironment, systemic immunity, and on the healthy mucosa surrounding cancer.MethodsPatients with a diagnosis of CRC operated on from 2015 to 2019 were retrospectively analyzed (METACCRE cohort). Expression of mRNA of immune surveillance‐related genes (PD‐L1, CD80, CD86, HLA I, and HLA II) in CRC primary cells treated with aspirin were extracted from Gene Expression Omnibus–deposited public database (GSE76583). The experiment was replicated in cell lines. The mucosal immune microenvironment of a subgroup of patients participating in the IMMUNOREACT1 (ClinicalTrials.gov NCT04915326) project was analyzed with immunohistochemistry and flow cytometry.ResultsIn the METACCRE Cohort, 12% of 238 patients analyzed were aspirin users. Nodal metastasis was significantly less frequent (p = .008) and tumor‐infiltrating lymphocyte infiltration was higher (p = .02) among aspirin users. In the CRC primary cells and selected cell lines, CD80 mRNA expression was increased following aspirin treatment (p = .001). In the healthy mucosa surrounding rectal cancer, the ratio of CD8/CD3 and epithelial cells expressing CD80 was higher in aspirin users (p = .027 and p = .034, respectively).ConclusionsThese data suggested that regular aspirin use may have an active role in enhancing immunosurveillance against CRC.
Funder
Associazione Italiana per la Ricerca sul Cancro
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