Nobel Prize for immune checkpoint inhibitors, understanding the immunological switching between immunosuppression and...

Immune checkpoint inhibitors (ICIs) are a revolutionary form of immunotherapy in cancer. However, the percentage of patients responding to therapy is relatively low, while adverse effects occur in a large number of patients. In addition, the therapeutic mechanisms of ICIs are not yet completely described.

The initial view (articles published in PubMed, Scopus, Web of Science, etc.) was that ICIs increase tumor-specific immunity. Recent data (collected from the same databases) suggest that the ICIs pharmacotherapy actually extends beyond the topic of immune reactivity, including additional immune pathways, such as disrupting immunosuppression and increasing tumor-specific autoimmunity. Unfortunately, there is no clear delimitation between these specific autoimmune reactions that are therapeutically beneficial, and nonspecific autoimmune reactions/toxicity that can be extremely severe side effects.

Immune checkpoint mechanisms perform a non-selective immune regulation, maintaining a dynamic balance between immunosuppression and autoimmunity. By blocking these mechanisms, ICIs actually perform an immunological reset, decreasing immunosuppression and increasing tumor-specific immunity and predisposition to autoimmunity. The predisposition to autoimmunity induces both side effects and beneficial autoimmunity. Consequently, further studies are necessary to maximize the beneficial tumor-specific autoimmunity, while reducing the counterproductive effect of associated autoimmune toxicity.