The American Cancer Society, in citing a study published in the Journal of the National Cancer Institute, suggests that low-dose of a the common aspirin could be useful in treating and preventing recurrence of several types of cancer, including esophageal, ovarian, stomach and prostate cancer. A new study published on Cell by Professor Caetano Reis e Sousa’s research group at The Francis Crick Institute suggests that aspirin could benefit cancer patients by boosting their immune system, rather than actively killing cancer cells.
Beside subverting the immune system activation by presenting checkpoint inhibitors – such as the PD-L1 or CTLA-4 ligands – on their surface, cancer cells are also capable of producing great amounts of inflammatory molecules like prostaglandins (PG) that act as chemo-attractants for the immune cells.
Although in a normal context this would be seen as a favorable outcome, resulting in a raise of the body temperature (fever) to fight bacterial or viral infections, in the tumor microenvironment an excessive production of PG has the adverse effect of inhibiting T cells.
This negative feedback loop, similarly to the mechanism at play with the checkpoint inhibitors PD-1/PD-L1 and CTLA-4/B7, prevents the overactivation of the immune system, which could be detrimental for a healthy body fighting infections. However these regulatory mechanisms have been highjacked by cancer cells at their advantage to escape the immune system and thrive at the expenses of the host.
The team lead by Prof. Reis e Sousa discovered that lab-grown melanoma skin cancer cells – originally taken from mice that were genetically prone to developing the disease, thanks to a fault in a gene called BRAF – are able to produce a great amount of one type of PG called prostaglandine E2 (PGE2). Moreover the researchers found that mice grafted with melanoma cells incapable of producing PGE2, because lacking the COX1 and COX2 enzymes function, develop slow growing tumors that are more easily detectable by the immune system. Similar patterns were observed in this study with preclinical models of bowel and breast cancer, suggesting that these observations could represent a rather common mechanism utilized by cancer cells to evade the immune system.
Aspirin is a known non-steroidal anti-inflammatory drug that inhibits that COX enzymes, preventing PG production. To test whether aspirin administration could reduce PGE2 levels and help driving a stronger immune response against the tumor, the researchers added aspirin to the drinking water of mice transplanted with melanoma cells.
Not surprisingly, treatment with aspirin alone had no effect on melanoma growth. However, when aspirin was given in combination with checkpoint inhibitors, which help unmasking the tumor cells so they can be recognized and targeted by the immune system, mice got rid of their tumors much quicker and developed a strong immune ‘memory’, meaning that their immune cells recognized and immediately destroyed the same type of cancer cells, even months after the first exposure.
The same immunotherapy-boosting power of aspirin was reported in this study for preclinical models of bowel cancer cells, even though with less potency.
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