Immunotherapy has revolutionized the treatment of cancer patients modifying the balance of the patients¿ immune system towards immune activation. Not all cancer patients respond to immunotherapy and that we need to integrate/combine the immune treatment with other strategies that can potentiate/synergize the otherwise useless immunotherapy treatment.
It is becoming clear that the fitness of the immune system is strictly correlated to the success of immunotherapy. Indeed, the identification of specific biomarkers able to define the wellness of the immune system appears to be mandatory to improve patients¿ selection.
CD137+ T cells subset appears one of the most promising biomarkers to define the ¿quality¿ of the immune activation and of the immune response. CD137 molecule identifies the naturally occurring antigen-specific T cells able to kill tumor cells upon expansion. The triggering of the CD137 pathway induces T cell division and survival, enhances the effector function of lymphocytes, protects against activation-induce T cell apoptosis, enhances the T cell mitochondrial metabolism and promotes the DNA demethylation of CD8 main genes. Several studies demonstrate the correlation between the frequency of circulating and infiltrating CD137+ lymphocytes and the clinical outcome.
This project aims to evaluate whether the CD137+cells subset could be used:
1. as a parameter to define the immunological fitness of cancer patients
2. as a biomarker to determine the success of immunotherapy
independently by tumor histotype and previous therapy.
Today we are knowledgeable about the enormous possibilities and potentiality of immunotherapy in the treatment of cancer. Despite the identification of several tumoral parameters, no biomarker has already been validated to select those cancer patients that could have beneficial effect from immunotherapy. In this research project, we propose to study the frequency of CD137+ cells as a biomarker that could define the ¿quality¿ of the immune activation and that could identify those patients more prone to receive beneficial effects from immunotherapy independently of tumor histotype. This finding could have a great impact on cancer patients that could be better selected for the right drug avoiding unnecessary, costly and toxic treatments and increasing the rate of cure.