Can aspirin prevent cancer?
Long-term daily aspirin intake may help prevent colorectal cancer development and progression but the mechanisms involved are still unclear.
Translated from the original Italian version.
Aspirin against colorectal cancer?
The multicentre study Immunoreact 7: Regular aspirin use is associated with immune surveillance activation in colorectal cancer, involves 14 Italian research groups and is coordinated by Dr Marco Scarpa (Department of Surgical, Oncological and Gastroenterological Sciences at the University Hospital of Padua) and is supported by the AIRC Foundation for Cancer Research. Marco Scarpa from the Department of Surgical, Oncological and Gastroenterological Sciences of the University Hospital of Padua aims to investigate the effect of acetylsalicylic acid on the tumour microenvironment, systemic immunity and the healthy mucosa surrounding colorectal cancer. Aspirin is usually taken in low doses to reduce the likelihood of certain cardiovascular diseases.
"In the first part of the study, we retrospectively analysed samples and data from patients with colorectal cancer who underwent surgery at the Azienda Ospedale Università di Padova between 2015 and 2019," explains Scarpa. "Then we analysed the mRNA expression of genes related to immune surveillance in primary colorectal cancer cells of patients, again in patients taking acetylsalicylic acid. In addition, we repeated these measurements experimentally in laboratory animals at the University of Padua and the Veneto Oncological Institute." The team finally investigated the immunological microenvironment of the healthy mucosa surrounding colorectal cancer in samples from a large subgroup of participats, to examine chronic intake of acetylsalicylic acid".
Compared to tissue samples from patients not taking the drug, samples from patients taking the drug showed less spread of cancer to the lymph nodes and greater infiltration of immune cells into the tumour. In laboratory analyses of colorectal cancer cells, exposure of these cells to acetylsalicylic acid led to an increase in the CD80 protein, a modulator of immune function. This increase appears to have improved the cells' ability to alert other immune cells to the presence of tumour-associated proteins. In support of this finding, the researchers also demonstrated that patients with colorectal cancer taking acetylsalicylic acid had higher CD80 protein levels in healthy rectal tissue, suggesting that the drug has an immune surveillance effect.
Aspirin impacted CD80 concentration, cytotoxic lymphocyte rations, and total T lymphocyte numbers
The data, Scarpa explained, "show that treatment with acetylsalicylic acid can increase CD80 expression, which improves the ability of colorectal cancer cells to actively present their tumour antigens to T lymphocytes. The latter are our defence cells that are responsible, among other things, for eliminating cancer cells as soon as their specific antigens are recognised". The team also noted that in patients with rectal cancer, both the concentration of CD80 protein in the epithelial cells, the ratio between cytotoxic lymphocytes, and the total number of T lymphocytes were higher in patients taking acetylsalicylic acid. "This suggests that acetylsalicylic acid exerts an immunosurveillance effect even on the normal mucosa and not just within the tumour when taken long term", he added.
The study results, which were published in the journal Cancer, show that acetylsalicylic acid can also be used to prevent and treat colorectal cancer in addition to its classic pharmacological mechanism of anti-inflammation.
The observations of the Immunoreact 7 study on the mechanism of action of aspirin relate to presumably healthy persons or persons with early-stage cancer, but not to patients with advanced stages of cancer. In the ASPREE study, the results of which were published in the Journal of National Cancer Institute in 2020, more than 19,000 people over the age of 70 were observed who either took acetylsalicylic acid or did not take it in low doses in the long term. Those who took the drug were not found to be more likely to be diagnosed with cancer than those who took a placebo.
- Simoni O, Scarpa M, Castagliuolo I, Stepanyan A, Angriman I, Kotsafti A, Nacci C, Scognamiglio F, Negro S, D'Angelo A, Chiminazzo V, Businello G, Ruffolo C, Salmaso R, Franzato B, Gruppo M, Pilati P, Scapinello A, Pozza A, Stecca T, Massani M, Cataldo I, Brignola S, Dei Tos AP, Ceccon C, Guzzardo V, Vignotto C, Facci L, Maretto I, Agostini M, Marchegiani F, Becherucci G, Zizzo M, Bordignon G, Merenda R, Pirozzolo G, Recordare A, Pozza G, Godina M, Mondi I, Verdi D, Lio CD, Laurino L, Saadeh L, Rivella G, Guerriero S, Romiti C, Portale G, Cipollari C, Spolverato YC, Noaro G, Cola R, Candioli S, Gavagna L, Ricagna F, Ortenzi M, Guerrieri M, Tagliente G, Tomassi M, Tedeschi U, Salmaso B, Buzzi G, Parini D, Prando D, Zuin M, Bergamo F, Zagonel V, Porzionato A, Cavallin F, Camillo BD, Cristoforo LD, Bao QR, Pucciarelli S, Bardini R, Spolverato G, Fassan M, Scarpa M; IMMUNOREACT Study Group. IMMUNOREACT 7: Regular aspirin use is associated with immune surveillance activation in colorectal cancer. Cancer. 2024 Apr 22. doi: 10.1002/cncr.35297. Epub ahead of print. PMID: 38644692.