Various studies have highlighted how the intake of aspirin reduce the incidence and mortality associated with colorectal cancer. A new all-Italian multicenter study, recently published in the journal Cancer, could give some clues as to why this happens. In fact, in this retrospective observational study, a lower number of lymph node metastases and lower grade tumors were observed in patients with colorectal cancer who took aspirin compared to those who did not take it.
The study, called IMMUNOREACT 7was coordinated by researchers from the University of Padua and supported by the AIRC Foundation.
Possible active role in enhancing immunosurveillance
According to the authors, the data suggest that regular aspirin intake could have an active role in enhancing immune surveillance against colorectal cancer. “In addition to the effect on tumor cells through inhibition of prostaglandin-endoperoxide synthase or cyclooxygenases, regular use of aspirin could have a direct role in improving immunosurveillance against colorectal cancer,” he said Marco Scarpacoordinator of the study.
The primary objective of the study was to analyze the effects of aspirin on the tumor microenvironment, on the immune system and also on the healthy mucosa surrounding the tumor.
Reduction of incidence and mortality with aspirin
According to recent epidemiological studies, colorectal cancer ranks third among new cancer diagnoses worldwide and second in number of deaths, and in the United States it has become the number one cause of cancer mortality among men.
«Numerous long-term follow-ups of randomized controlled trials on aspirin have shown that daily use of aspirin reduces the incidence and mortality of colorectal cancer, after a latency period of approximately 8-10 years and overall mortality for cancer from 5 years to 20 years, as well as reducing deaths from several other types of cancer,” the authors write. “We wanted to explore whether, in addition to the well-known cyclooxygenase effect, aspirin could have some immunological effect that could better explain the clinical and epidemiological data,” Scarpa said.
The IMMUNOREACT 7 study
In the study, which involves 14 Italian research groups, three different cohorts of patients were analysed. The first included consecutive patients treated for colorectal cancer at the General Surgery Unit of the University Hospital of Padua from 2015 to 2019 (METACCRE cohort). The other two used all consecutive patients from the retrospective and prospective cohorts of the multicenter IMMUNOREACT 1 project, which is studying patients with early-stage rectal cancer for whom information on aspirin use was known.
Aspirin users were defined as all those who had started taking low-dose aspirin at least one year before the diagnosis of cancer.
The METACCRE cohort included 238 patients, 12% of whom were aspirin users. The retrospective IMMUNOREACT cohort included 130 patients, of which 22% were users of acetylsalicylic acid, while the prospective cohort consisted of 82 patients, of which 19.5% were aspirin users.
Fewer lymph node metastases and more lymphocytes infiltrating the tumor
In the METACCRE cohort, patients using aspirin had significantly lower tumor grading (P = 0.02), fewer lymph node metastases (P = 0.008), and higher tumor-infiltrating lymphocyte rates (P = 0 ,02).
Additionally, aspirin-using patients had an overall reduced neutrophil-to-lymphocyte ratio (P 0.042), which was further reduced in patients whose tumors were deficient in the DNA mismatch repair system (P = 0.008) and in those with mutations of the BRAF gene (P = 0.009).
The analysis showed that patients with ascending (right) colon cancer took aspirin more frequently and had lower tumor grading, and a reduced number of lymph node metastases and metastatic lymph nodes.
PD-L1 (P = 0.01) and CD80 (P = 0.007) mRNA expression was also significantly higher with aspirin use.
In the IMMUNOREACT retrospective cohort it was observed that “in the healthy mucosa surrounding the rectal tumor, the rate of lymphocytes capable of destroying the mutated cells and epithelial cells capable of activating them was higher among aspirin users”, said Scarpa .
Limitations of the study
Among the limitations of the study, the authors cite the lack of information on the duration of aspirin use and the self-reported nature of the data.
Scarpa pointed out in an interview that the main side effects of aspirin are well known and must be balanced with the potential benefits. “We believe that we should await the results of other studies, such as the NeoAspMet study on the use of aspirin and metformin in neoadjuvant therapy of rectal cancer, before formally proposing a new indication for aspirin therapy,” she said.
The author said he hoped that further clinical evidence could be obtained on recurrence and survival rates (in aspirin-using colorectal cancer patients, ed.), particularly in subpopulations of patients, to improve current information on dosage and who can benefit most from the drug.
«This is a study that investigates what has always been considered a mere side effect of aspirin, that is, the pro-inflammatory effect on the mucosa of the digestive tract», added Scarpa. «Perhaps we can use these side effects in the prevention and treatment of colorectal cancer, provided we find adequate doses and manage to balance the other side effects» she concluded.
Bibliography
O. De Simoni et al. Cancer. IMMUNOREACT 7: Regular aspirin use is associated with immune surveillance activation in colorectal cancer. Cancer 2024 read
