Fig. 6

Challenges in the clinical application of neoantigen TCR-T-cell therapy. a Low neoantigen load results in a lack of suitable neoantigen targets. b At present, the accuracy of neoantigen prediction technology is limited. c Downregulation of MHC expression causes tumor cells to lose neoantigen targets. d The loss of pMHC molecules leads to the interruption and reduction of neoantigen presentation. e The expression of adhesion molecules and stroma-rich and abnormal blood vessels in tumor tissues is downregulated, which limits the effective penetration of T cells. f Immunosuppressive tumor microenvironments inhibit T-cell function. g The technical bottleneck of ACT leads to the production of neoantigen-specific T cells. h Tumor heterogeneity leads to the singleness of specific tumor therapeutic targets and the absence of universal neoantigen targets. i The neoantigen epitopes developed thus far are mainly for HLA-A2 targets. j Safety of TCR-T-cell therapy itself