Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity

摘要: The immune response plays an important role in staving off cancer; however, mechanisms of immunosuppression hinder productive anti-tumor immunity. T cell dysfunction or exhaustion tumor-bearing hosts is one such mechanism. PD-1 has been identified as a marker exhausted cells chronic disease states, and blockade PD-1–PD-1L interactions shown to partially restore function. We have found that immunoglobulin mucin (Tim) 3 expressed on CD8+ tumor-infiltrating lymphocytes (TILs) mice bearing solid tumors. All Tim-3+ TILs coexpress PD-1, Tim-3+PD-1+ represent the predominant fraction infiltrating exhibit most severe phenotype defined by failure proliferate produce IL-2, TNF, IFN-γ. further find combined targeting Tim-3 pathways more effective controlling tumor growth than either pathway alone.