The modulation of the apoptotic pathways to reverse immune resistance presents a unique opportunity to improve the outcome of current anticancer treatment strategies. Even though immunotherapy has not been successful in killing tumor cells, due to the profound tumor immuneresistance to apoptosis, immunosensitizing agents that modulate signaling molecules involved in the immune-mediated apoptosis may enhance tumor killing and improve the efficacy of immunotherapy. Sensitizing agents of various kinds have been reported to sensitize tumor cells to death-ligand apoptosis such as chemotherapeutic drugs, pharmacologic inhibitors of survival pathways, cytokines, nitric oxide donors, specific inhibitors (chemicals or siRNA) of anti-apoptotic gene products, anti-receptor antibodies, etc. The description of these various sensitizing agents and their mechanisms of actions are outside the scope of this review. However, representative sensitizing agents that have been used by us will be briefly described below.
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