In the tumor microenvironment, infiltrating cytotoxic T cells become dysfunctional when engaging with killing tumor cells. One reason for this dysfunctionality is T cells do not receive the correct signals from their environment, causing inhibition of their function. Many of the new immunotherapies proving successful in the clinic – anti-PD1 and anti-CTLA-4 checkpoint blockade – target this pathway to turn T cells back on and improving their function. While these therapies are very promising, they do not work in all patients, leaving the door open for improvements.
Our lab is interested in exploring how other T cell signaling pathways may be utilized to improve T cell function, looking specifically at metabolic function. If we can hit the right T cell signaling pathway to improve T cell metabolic function, can we improve the efficacy of checkpoint blockade?