Aspirin and colorectal cancer: Italian study reveals why it can have a protective effect

There is (also) the influence of the immune system behind the protective effect of aspirin against colorectal cancer. This is demonstrated today by a study just published in Cancer, the all-Italian journal of the American Cancer Society. According to the results, in fact, the daily use of acetylsalicylic acid seems to be correlated, in patients operated on for colorectal cancer, to a greater response of the immune cells and a lower spread of the tumor. But let’s go in order.

A well-known effect

That aspirin is related to a reduction in the risk of developing colorectal cancer has been known for over 30 years. Many studies have been conducted, most of which are observational and mainly on populations who were already taking acetylsalicylic acid for cardiovascular reasons. To date, however, the accumulated evidence has not led to changes in the indications for this drug, which – like all drugs – has side effects that must be carefully weighed in an analysis of the relationship between risks and benefits.

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I study

The new study, carried out by the University of Padua with the Padua University Hospital and funded by the AIRC Foundation for cancer research, is part of the multicenter Immunoreact project (acronym for IMMUNOlogical microenvironment in the REctal Adenocarcinoma Treatment and includes a series of studies focused on the immune microenvironment in colorectal tumors). “We wanted to investigate whether and how the daily intake of aspirin modifies the immune microenvironment of the healthy tissue surrounding the tumor in patients,” he explains to Oncoline Marco Scarpa, lead author of the work. It is therefore an observational study and was carried out in three steps. In the first phase, tumor samples from approximately 240 patients who underwent surgery between 2005 and 2019 were analyzed to understand if there were differences between those who took aspirin – 12% – and those who did not: “We observed – resumes Scarpa – that those who used aspirin had fewer metastases to the lymph nodes, i.e. less spread of the disease, and had a greater infiltration of immune cells within the tumor”.

In the second phase, the researchers analyzed the behavior of immune cells extracted from colorectal cancer and cultured with aspirin, finding that they expressed more co-stimulatory molecules that activate T lymphocytes, in particular a protein called CD80. In the third phase, Scarpa and colleagues returned to the healthy tissues surrounding the neoplasm of their patients, also verifying in this case that in the subgroup taking aspirin there was a greater expression of CD80 and, consequently, a greater presence of infiltrating T lymphocytes the tumor.

A pro-immune action

“We expected the fact that aspirin increases the immune response at the gastrointestinal level – continues the researcher – It is well known, in fact, that in patients with gastrointestinal pathologies such as ulcerative colitis, aspirin causes an increase in the immune response which is absolutely unwanted in this autoimmune disease. We then hypothesized that this side effect could turn into an advantage in the presence of cells that begin to mutate, because it could help the immune system recognize them as foreign. That is, there appears to be a complementary pro-immune surveillance effect of aspirin, which works better in the first phase of carcinogenesis. And in fact other studies have shown a protective action of the anti-inflammatory drug in people with familial intestinal polyposis. However, there are many aspects that must be taken into consideration: this approach does not always and not in all cases give the same results, so it is not possible to bring it into clinical practice at present.” It should in fact be underlined that in this study no interventions or modifications to therapies were made and that no recommendation can be derived from this, in any sense, on the use of aspirin.

Caution is needed: taking aspirin as prevention is not recommended

“Today in clinical practice we cannot use acetylsalicylic acid as a preventive drug for colorectal cancer: there is no guideline that recommends it – he confirms Nicholas Sylvester, national secretary of the Italian Association of Medical Oncology (Aiom) and Professor of Oncology at the University of Messina – Obviously the data in scientific literature regarding its correlation with the reduction in incidence and recurrence of this neoplasm – but also of others, mainly of the gastrointestinal tract – are very intriguing, so much so that this possible relationship was also included in a note from the Italian Medicines Agency in 2018. But these data must be interpreted as a recognition of the potential protective effect of acetylsalicylic acid, certainly not a authorization for use for the prevention of this tumor. It is essential to clarify: the drug does not have this indication and has possible side effects related to its antiplatelet activity which must be taken into account. It is therefore advisable to be very careful about the message you transmit. Having said this – concludes Silvestris – the new study provides important new information to better interpret the epidemiological data that we have been observing for 25 years in patients with cardiovascular diseases and that we will be able to use in the future”.