The genetic and epigenetic aberrations that underlie immune resistance lead to tumors that are refractory to clinically established and experimental immunotherapies,including monoclonal antibodies and T cell-based the...The genetic and epigenetic aberrations that underlie immune resistance lead to tumors that are refractory to clinically established and experimental immunotherapies,including monoclonal antibodies and T cell-based therapies.From various forms of cytotoxic T cells to small molecule inhibitors that revamp the tumor microenvironment,these therapies have demonstrated notable responses in cancer models and a resistant subset of cancer patients,used both alone and in combination.However,even current approaches,such as those targeting checkpoint molecules,tumor ligands,and involving gene-related therapies,present a challenge in non-responding patients.In this perspective,we discuss the most common mechanisms of immune resistance,including tumor heterogeneity,tumor ligand and major histocompatibility complex modulation,anti-apoptotic pathways,checkpoint inhibitory ligands,immunosuppressive cells and factors in the tumor microenvironment,and activation-induced cell death.In addition,we discuss the strategies designed to circumvent these resistance pathways to showcase the potential of emerging technologies in battling the rise of resistance.展开更多
文摘The genetic and epigenetic aberrations that underlie immune resistance lead to tumors that are refractory to clinically established and experimental immunotherapies,including monoclonal antibodies and T cell-based therapies.From various forms of cytotoxic T cells to small molecule inhibitors that revamp the tumor microenvironment,these therapies have demonstrated notable responses in cancer models and a resistant subset of cancer patients,used both alone and in combination.However,even current approaches,such as those targeting checkpoint molecules,tumor ligands,and involving gene-related therapies,present a challenge in non-responding patients.In this perspective,we discuss the most common mechanisms of immune resistance,including tumor heterogeneity,tumor ligand and major histocompatibility complex modulation,anti-apoptotic pathways,checkpoint inhibitory ligands,immunosuppressive cells and factors in the tumor microenvironment,and activation-induced cell death.In addition,we discuss the strategies designed to circumvent these resistance pathways to showcase the potential of emerging technologies in battling the rise of resistance.
