Potential targets | Mechanisms | Potential targets | Therapeutic intervention |
---|---|---|---|
Malignant cells | Inactivation of antigen presentation | ADAR1 [163] | – |
Depletion and dysfunction of CD8+ T cells | MUC1-C [164] | – | |
Macrophage exhaustion | PDIA5 [165] | – | |
Inhibition of ICOSL+ B-cells | CD55 [166] | – | |
Exhausted CD8+ T cells | Dysfunction of T cells | PMEL, TYRP1, and EDNRB [158] | – |
CD8+ T cells | Transcriptional regulators determining T cell fates | FOXO1, KDM5B, MAF, IKZF2, SOX4, and BCL3 [110] | – |
NK cells | Inhibitory and costimulatory molecules | TNFRSF18 (GITR), CD96, and KIR2DL4 [110] | – |
HIF-1α, reducing antitumor effects | HIF-1α inhibitor [167] | – | |
Immature myeloid cells | Immune suppression | – | Tyrosine kinase inhibitor cabozantinib [168] |
TREM2+ TAMs | Associated with T-cell response | – | |
PD-L1+ TAMs and APOE+ G-MDSCs | T-cell inhibition induced by TAMs and G-MDSCs | – | anti-CSF1R and anti-Ly6G antibodies [157] |
vCAFs/ICC | Enhancement of malignancy | IL-6 [162] | – |
CAFs/malignant cells | Immune evasion | PVR-TIGIT, LGALS9-HAVCR2, and TGF-β-TGF-βR axis [169] | – |
PLVAP/VEGFR2 ECs/FOLR2 TAMs | Onco-foetal reprogramming of the tumour ecosystem | VEGF/NOTCH [170] | – |
Malignant cells/IL-17-producing T cells | Activation of angiogenesis and suppression of CD8+ T cells | – | IL-17 blockade [171] |
CXCL13+ T cells/B cells | Associated with prognosis | CXCL13/CXCR5 [172] | – |