Immune system : a firewall against cancer
The immune system protects the body against external infection, but not only. Part of its role is also to detect uncontrolled proliferating cells like cancer cells. This is done through the recognition of specific macromolecules (proteins, glycoproteins) often expressed at the surface of cancer cells. However, in certain conditions abnormal cells can evade the immune system leading to the development of cancer.
Immuno-oncology therapeutic strategies
The purpose of immuno-oncology treatments is to boost the immune system turning immunodepressed or immunosuppressed tumor microenvironment into an immunocompetent one. Such conversion is possible by blocking the immunosuppressive pathways engaged by some tumors and mediated by immune checkpoints. Immune checkpoints are consisting in a panel of receptors and ligands both expressed at the surface of cancer cells and immune cells and leading to inactivation of anti-tumoral immune cells or activation of protumoral immune cells. Depending on the immunosuppressive strategy in presence, conversion of immunosuppressive into an immunocompetent tumor microenvironement can be achieved either by blocking inhibitory checkpoints or by activating the stimulatory checkpoints. Alternatively, novel cellular approaches consisting in collecting T cells from patients, genetically engineering it to trigger immune response before reinjecting them to patients. Such approach named CAR-T cell therapy showed also great promises.
Immune checkpoint inhibitors
Inhibitory checkpoints are negative regulators of the immune system playing a key role in the control of the immune response. The most representatives are PD-1 and CTLA-4, targets which have led to the commercialization of the first immune checkpoint inhibitors ( IPI ) as powerful cancer treatments for multiple tumors ( anti-PD-1 immunotherapy such as PREMBO or NIVO ). The discovery of such IPI pioneering decades of basic science investigations in immuno-oncology were rewarded by the Nobel Prize in Physiology or Medicine attributed to Pr. James P. Allison and Pr. Tasuku Honjo in 2018. Further examples of inhibitory checkpoints belonging to the GPCR family consist in adenosine A2A and A2B receptors, or the prostaglandin E2 EP4R.
Stimulatory checkpoint activators
Stimulatory checkpoints are positive regulators of the immune system that can be activated in order to boost the anti-cancer immune response. Examples of stimulatory checkpoints developed as novel immuno-oncology therapies include OX40 or CD40.