Trafficking of antigen-specific cytotoxic T cells into the tumor is critical for an efficient immune response against cancer cells. The recruitment of tumor-specific T cells that express many chemokine receptors on their surface, will reflect the chemokines secreted by the tumor microenvironment. Physiological lymphocyte migration is a regulated systematic process relying on the involvement of selectins, chemokine receptors and integrins. Chemokine receptor activation by chemokines induces intracellular pathway cascades that lead to the expression and activation of integrins. To guarantee infiltration of the relevant lymphocytes into the target tissues, T cell priming induces the expression of a set of chemokine receptors, integrins and selectins that is unique for each tissue. The expression of chemokine receptors on the T cells mirrors the effector function on T cells. Various chemokines and chemokine receptors play a role in tumor immunity. For example, CXCR3 is preferentially expressed on IFN producing type 1 T cells (Th1); CCR6 on IL-17 producing cells (Th17) and CCR4 on IL-4 producing cells (Th2).
Thus, impaired chemokine expression at the tumor site favors immune evasion of tumor cells.
Evaluating the role chemokines and chemokine receptors play in T cell infiltration in combination with checkpoint therapy such as PD-1 and CTLA-4 may provide additional therapeutic strategies.
Screen for chemokines and chemokine receptors involved in lymphocyte infiltration
Discover chemokines and immune checkpoint interactions
Combination studies of chemokines and immune checkpoint blockade
Engineered chemokine receptors and chemokines in our HLA-matched CTL and tumor lines