Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.
Azienda Ospedale Università di Padova, Padova, Italy.
Cancer. 2024 Jul 1;130(13):2272-2286. doi: 10.1002/cncr.35297. Epub 2024 Apr 22.
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.
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.
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).
These data suggested that regular aspirin use may have an active role in enhancing immunosurveillance against CRC.
长期每日使用阿司匹林可降低结直肠癌（CRC）的发病率和死亡率。本研究旨在分析阿司匹林对肿瘤微环境、全身免疫以及癌症周围健康黏膜的影响。
回顾性分析了 2015 年至 2019 年接受手术治疗的 CRC 患者（METACCRE 队列）。从基因表达综合数据库（GEO）中提取接受阿司匹林治疗的 CRC 原代细胞中与免疫监测相关基因（PD-L1、CD80、CD86、HLA I 和 HLA II）的 mRNA 表达。该实验在细胞系中进行了复制。采用免疫组化和流式细胞术分析参与 IMMUNOREACT1 项目（ClinicalTrials.gov NCT04915326）的亚组患者的黏膜免疫微环境。
在 METACCRE 队列中，238 例分析患者中有 12%为阿司匹林使用者。与非使用者相比，阿司匹林使用者的淋巴结转移明显较少（p=0.008），肿瘤浸润淋巴细胞浸润更高（p=0.02）。在 CRC 原代细胞和选定的细胞系中，阿司匹林处理后 CD80 mRNA 表达增加（p=0.001）。在直肠癌周围的健康黏膜中，阿司匹林使用者的 CD8/CD3 比值和上皮细胞表达 CD80 的比例更高（p=0.027 和 p=0.034）。
这些数据表明，规律使用阿司匹林可能在增强针对 CRC 的免疫监测方面发挥积极作用。
