Control of established melanoma by CD27 stimulation is associated with enhanced effector function and persistence, and reduced PD-1 expression, of tumor infiltrating CD8+ T cells

摘要: The immune response to the tumor can be enhanced by targeting costimulatory molecules on T cells. As CD70-CD27 axis plays an important role in activation, survival, and differentiation of lymphocytes, we have examined efficacy agonistic anti-CD27 antibodies as monotherapies for established melanoma a murine model. We show that this approach leads substantial reduction outgrowth both experimental lung metastases subcutaneous tumors. Anti-CD27 treatment supports maintenance tumor-specific CD8(+) cells within tumor, reduces frequency FoxP3-expressing CD4(+) tumors, potentiates ability NK1.1(+) infiltrating secrete IFN? upon coculture with effector function correlated lower levels PD-1 expression from anti-CD27-treated mice. Despite modulating effect multiple cell types, only were absolutely required control. dispensable, whereas needed during early stages growth but not effectiveness anti-CD27. Thus, CD27-mediated costimulation provides potent boost aspects endogenous responses may exploited enhance immunity.