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. 2024 Jul 1;130(13):2272-2286.
doi: 10.1002/cncr.35297. Epub 2024 Apr 22.

IMMUNOREACT 7: Regular aspirin use is associated with immune surveillance activation in colorectal cancer

Ottavia De Simoni  1 , Melania Scarpa  1 , Ignazio Castagliuolo  2 , Astghik Stepanyan  2 , Imerio Angriman  2 , Andromachi Kotsafti  1 , Camilla Nacci  2 , Federico Scognamiglio  2 , Silvia Negro  2 , Antonella D'Angelo  2 , Valentina Chiminazzo  2 , Gianluca Businello  3 , Cesare Ruffolo  2 , Roberta Salmaso  2 , Boris Franzato  1 , Mario Gruppo  1 , Pierluigi Pilati  1 , Antonio Scapinello  1 , Anna Pozza  4 , Tommaso Stecca  4 , Marco Massani  4 , Ivana Cataldo  4 , Stefano Brignola  4 , Angelo Paolo Dei Tos  2 , Carlotta Ceccon  2 , Vincenza Guzzardo  2 , Chiara Vignotto  2 , Luca Facci  2 , Isacco Maretto  2 , Marco Agostini  2 , Francesco Marchegiani  2 , Giulia Becherucci  5 , Maurizio Zizzo  6 , Giovanni Bordignon  7 , Roberto Merenda  7 , Giovanni Pirozzolo  7 , Alfonso Recordare  7 , Giulia Pozza  2 , Mario Godina  7 , Isabella Mondi  7 , Daunia Verdi  7 , Corrado Da Lio  7 , Licia Laurino  7 , Luca Saadeh  2 , Giorgio Rivella  2 , Silvio Guerriero  8 , Chiara Romiti  8 , Giuseppe Portale  9 , Chiara Cipollari  9 , Ylenia Camilla Spolverato  9 , Giulia Noaro  9 , Roberto Cola  9 , Salvatore Candioli  5 , Laura Gavagna  5 , Fabio Ricagna  5 , Monica Ortenzi  10 , Mario Guerrieri  10 , Giovanni Tagliente  11 , Monica Tomassi  11 , Umberto Tedeschi  11 , Beatrice Salmaso  3 , Gianluca Buzzi  3 , Dario Parini  3 , Daniela Prando  3 , Matteo Zuin  7 , Francesca Bergamo  1 , Vittorina Zagonel  1 , Andrea Porzionato  12 , Francesco Cavallin  13 , Barbara Di Camillo  12 , Loretta Di Cristoforo  14 , Quoc Riccardo Bao  2 , Salvatore Pucciarelli  2 , Romeo Bardini  2 , Gaya Spolverato  2 , Matteo Fassan  1   2 , Marco Scarpa  2 ; IMMUNOREACT Study Group
Affiliations
Free article

IMMUNOREACT 7: Regular aspirin use is associated with immune surveillance activation in colorectal cancer

Ottavia De Simoni et al. Cancer. .
Free article

Abstract

Background: Long-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.

Methods: Patients 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.

Results: In 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).

Conclusions: These data suggested that regular aspirin use may have an active role in enhancing immunosurveillance against CRC.

Keywords: CD8; CD80; aspirin; colorectal cancer; nodal metastasis; tumor infiltrating lymphocytes.

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