Studies on aspirin keep coming. For decades, studies found that persons taking aspirin frequently have a lowered risk of developing colorectal (colon) cancer, and that they are less likely to die if they do develop colorectal cancer. A recent study confirmed these aspirin findings and looked at what is occurring.
Aspirin appears to boost or activate the immune system, which helps explain its protective effect in colorectal cancer. Clinical trials are going on now to test whether and how aspirin can be part of colorectal cancer treatment.
From Medscape: How Aspirin May Lower Risk for Colorectal Cancer
A 2020 meta-analysis, for instance, found that 325 mg of daily aspirin — the typical dose in a single tablet — conferred a 35% reduced risk of developing CRC, and a highly cited The Lancet study from 2010 found that a low dose of daily aspirin reduced the incidence of colon cancer by 24% and colon cancer deaths by 35% over 20 years.
The evidence surrounding aspirin and CRC is so intriguing that more than 70,000 people are currently participating in more than 2 dozen clinical studies worldwide, putting aspirin through its paces as an intervention in CRC.
But what, exactly, is aspirin doing?
We know that aspirin inhibits cyclooxygenase (COX) enzymes — COX-1 and COX-2, specifically — and that the COX-2 pathway is implicated in the development and progression of CRC, explained Marco Scarpa, MD, PhD, staff surgeon at the University of Padova in Padova, Italy.
"However, the new thing we've found is that aspirin may have a direct role in enhancing immunosurveillance," Scarpa told Medscape Medical News.
In April, Scarpa's team published a paper in Cancer describing a mechanism that provides deeper insight into the aspirin-CRC connection.
Scarpa heads up the IMMUNOREACT study group, a collaboration of dozens of researchers across Italy running studies on immunosurveillance in rectal cancer. In the baseline study, IMMUNOREACT 1, the team created and analyzed a database of records from 238 patients who underwent surgery for CRC at the Azienda Ospedale Università di Padova, Padova, Italy, from 2015 to 2019.
Using the same database, the latest findings from IMMUNOREACT 7 focused on the fate of the 31 patients (13%) who used aspirin regularly.
The researchers found that regular aspirin use did not appear to affect colorectal tumor stage at diagnosis, but tumor grading was significantly lower overall, especially in patients with BRAF mutations. Regular aspirin users were also less likely to have nodal metastases and metastatic lymph nodes, and this effect was more pronounced in patients with proximal (right-sided) colon cancer vs distal (left-sided).
Most notably, IMMUNOREACT 7 revealed that aspirin has beneficial effects on the CRC immune microenvironment.
The team found that aspirin directly boosts the presence of antigens on gastrointestinal epithelial tumor cells, which can direct the body's immune response to combat the cancer.
At a macro level, the aspirin users in the study were more likely to have high levels of tumor-infiltrating lymphocytes (TILs). Scarpa's team had previously shown that high levels of CD8+ and CD3+ TILs were predictive of successful neoadjuvant therapy in rectal cancer.
Cytotoxic CD8+ T cells are central to the anticancer immune response, and in the latest study, a high ratio of CD8+/CD3+ T-cells was more common in aspirin users, suggesting a stronger presence of cancer-killing CD8+ cells. Expression of CD8 beta+, an activation marker of CD8+ cells, was also enhanced in aspirin users.
The most significant discovery, according to Scarpa, was that aspirin users were more likely to show high expression of CD80 on the surface of their rectal epithelial cells.
CD80 is a molecule that allows T cells to identify the tumor cell as foreign and kill it. Although cancer cells can downregulate their CD80 to avoid detection by T cells, the study suggests that aspirin appears to help foil this strategy by boosting the production of CD80 on the surface of the tumor cells.
Overall, these new data suggest that aspirin helps activate the immune system, which helps explain its potential chemopreventive effect in CRC.
Despite the small patient numbers in the study, Kerr felt encouraged by the IMMUNOREACT analysis. "It's a plausible piece of science and some quite promising work on the tumor immune microenvironment and the effects of aspirin on it," Kerr said in a recent commentary for Medscape Medical News.