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Aspirin may have ‘direct role’ in augmenting the immune system to fight colorectal cancer

Aspirin may have ‘direct role’ in augmenting the immune system to fight colorectal cancer

Whereas previous studies have shown aspirin use decreases incidence and mortality of colorectal cancer, researchers may now have insight into why this occurs, according to study results published in Cancer.

Individuals who used aspirin had fewer nodal metastases and increased tumor-infiltrating lymphocyte penetration, and expressed more proteins to help the body ward off the disease in the observational study.

Quote from Marco Scarpa, MD, PHD

“Besides the effect on cancer cells through the inhibition of prostaglandin–endoperoxide synthase or cyclooxygenase enzymes, regular aspirin use may have a direct role in enhancing immunosurveillance against colorectal cancer,” Marco Scarpa, MD, PhD, staff surgeon at University of Padova in Italy, told Healio.

Background and methodology

Healio previously reported colorectal cancer (CRC) produced the third most cancer diagnoses globally and second most deaths, and it has become No. 1 in cancer mortality in the U.S. among men. However, aspirin can have a significant role in decreasing those numbers.

“Many long‐term follow‐ups of randomized controlled trials of aspirin versus control have shown that daily aspirin use reduces incidence and mortality from CRC, after a latent period of approximately 8 to 10 years and total cancer mortality from 5 years to 20 years, with reductions in deaths from several other cancers,” researchers wrote.

“We wanted to explore whether, besides the well-known effect on cyclooxygenase enzymes, aspirin might have some immunologic effect that could further explain the clinical and epidemiologic data,” Scarpa said.

Researchers used three different cohorts for their study.

The first included consecutive patients treated for colorectal cancer at Chirurgia Generale Unit, Azienda Ospedale Università di Padova, Italy, from 2015 to 2019 (METACCRE). The other two used all of the consecutive patients of the retrospective and prospective cohorts of multicenter IMMUNOREACT 1 project, which is studying patients with early rectal cancer, who had information on aspirin use.

They defined aspirin users as any individual who started using low-dose aspirin at least 1 year prior to diagnosis.

The METACCRE cohort consisted of 238 patients (12% aspirin users). The IMMUNOREACT retrospective cohort consisted of 130 participants (22% aspirin users) and the prospective cohort had 82 (19.5% aspirin users).

Results and next steps

In the METACCRE cohort, individuals who used aspirin had significantly lower tumor grading (P = .02), fewer nodal metastases (P = .008) and higher rates of tumor=infiltrating lymphocyte infiltration (P = .02).

Additionally, aspirin users had reduced neutrophil to lymphocyte ratios overall (P = .042), and that number dipped further in patients with mismatch repair gene deficient–type tumors (P = .008) and in those with BRAF mutations (P = .009).

Individuals who had right colon cancer took aspirin more often, and those patients had lower tumor grading, reduced nodal metastases and metastatic lymph nodes.

PD-L1 (P = .01) and CD80 mRNA expression (P = .007) drastically increased with aspirin use as well.

In the IMMUNOREACT retrospective cohort, “in the healthy mucosa surrounding rectal cancer, the rate of lymphocytes that can destroy mutated cells and epithelial cells that can activate them was higher in aspirin users,” Scarpa said.

Study limitations included lack of information on duration of aspirin use, and the self-reported nature of the data.

“Aspirin’s main side effects are well known and should be balanced with potential benefits,” Scarpa said. “We think that we should wait for the results of [other] trials, such as the NeoAspMet trial on the use of aspirin and metformin in the neoadjuvant therapy for rectal cancer, before formally proposing a new indication for aspirin therapy.”

Scarpa hopes more clinical evidence on recurrence and survival, particularly on subpopulations, can be obtained to enhance current information on dosing and who benefits the most.

“This is a study that investigates what has always been considered a mere side effect of aspirin, the proinflammatory effect on the digestive tract mucosa,” Scarpa said. “Maybe we can use these side effects in the prevention and treatment of colorectal cancer, provided that we find adequate doses and we can balance the other side effects.”

April 24, 2024

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