Ignacio Melero
Professor of Immunology at the University of Navarra, CIMA researcher and co-director of the Department of Immunology and Immunotherapy at the Clínica Universidad de Navarra.
This article adds interesting evidence to a recurring theme in cancer immunotherapy. Several prostaglandins, lipid mediators of inflammation, are immunosuppressive in the context of tumours. This has been demonstrated with prostaglandin E2 produced by the tumour cells themselves in pioneering work by the groups of George Coukos (Lausanne) and Santiago Zelenay (Manchester). Another of these prostaglandins, called thromboxane A2, is produced by activated platelets and, in fact, is involved in platelet aggregation to form thrombi. Prostaglandin synthesis can be blocked by drugs such as aspirin, which inhibit a crucial enzyme in its synthesis.
In this interesting piece of work published in Nature, the authors from the University of Cambridge are able to demonstrate an interesting mechanism according to which platelets, by producing thromboxane A2, are able to interfere with the activation of immune system cells (T lymphocytes) capable of recognising and destroying tumours. This phenomenon is especially relevant for tumour cells that enter the bloodstream with the risk of generating metastasis. In this context, tumour cells are particularly susceptible to elimination by cells of the immune system and appear to use thromboxane A2-producing platelets as bodyguards.
The deductive research is brilliant. They had previously discovered a factor that facilitates metastasis in mice and in the screening a regulatory protein appeared that is relatively unknown but whose levels increase with thromboxane A2. From there, they found that thromboxane favours metastasis through an immunosuppressive mechanism and through this experimental route they observed that aspirin and other prostaglandin synthesis inhibitors decrease the efficiency of metastasis.
What is missing from the article is the demonstration of the same phenomenology between human platelets and lymphocytes. The data suggest that we should explore whether low-dose aspirin (antiplatelet dose) consumption decreases the likelihood of metastasis in cancer patients or whether patients receiving aspirin are less frequently diagnosed at the metastatic stage.
Previous studies, to which this one is now added, give reasons for carrying out clinical trials in which the synthesis of prostaglandins is blocked in the context of the immunotherapy treatments that we routinely apply to patients.