摘要
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.
