Driver mutations and the immunological TME
| Study . | Driver mutation . | Disease . | Immune correlates . |
|---|---|---|---|
| Vadakekolathu et al9 | RUNX1, TP53 | AML | Higher TIS, IFN signaling, and cytotoxicity scores relative to patients with favorable or intermediate-risk AML |
| Vadakekolathu et al35 | TP53 | AML | High expression of IFNG, FOXP3, immune checkpoints, markers of immune senescence, and phosphatidylinositol 3-kinase-Akt and NF-κB signaling intermediates |
| Sallman et al36 | TP53 | AML | Reduced numbers of BM-infiltrating OX40+ cytotoxic T cells and helper T cells Decreased ICOS+ and 4-1BB+ NK cells Expansion of myeloid-derived suppressor cells and Treg cells Increase of PD-L1 expression in HSCs |
| Dufva et al8 | TP53 | AML | High cytolytic score (especially in MDS-like cases) and high expression of PD-L1 |
| NPM1 | AML | Increased expression of VISTA and ULBP1 (NKG2D ligand) | |
| RUNX1 | AML | High expression of B-cell–associated markers (BTN2A2, SLAMF7, and LY9) in addition to HLA II | |
| Abbas et al37 | chr7/7q loss | AML | Higher Treg and CD8+ T-cell infiltration, downregulation of IFN-γ pathway genes, and worse survival compared with AML cases with intact chr7/7q |
| Yeaton et al38 | TET2 | AML | Emergence of inflammatory monocyte-like cells during progression to myeloid transformation |
| Notarangelo et al39 | IDH1/IDH2 | Human IDH-mutant cancers | Acute but reversible inhibition of CD8+ T-cell proliferation, cytotoxicity, and IFN-γ signaling by oncometabolite d-2HG |
| Study . | Driver mutation . | Disease . | Immune correlates . |
|---|---|---|---|
| Vadakekolathu et al9 | RUNX1, TP53 | AML | Higher TIS, IFN signaling, and cytotoxicity scores relative to patients with favorable or intermediate-risk AML |
| Vadakekolathu et al35 | TP53 | AML | High expression of IFNG, FOXP3, immune checkpoints, markers of immune senescence, and phosphatidylinositol 3-kinase-Akt and NF-κB signaling intermediates |
| Sallman et al36 | TP53 | AML | Reduced numbers of BM-infiltrating OX40+ cytotoxic T cells and helper T cells Decreased ICOS+ and 4-1BB+ NK cells Expansion of myeloid-derived suppressor cells and Treg cells Increase of PD-L1 expression in HSCs |
| Dufva et al8 | TP53 | AML | High cytolytic score (especially in MDS-like cases) and high expression of PD-L1 |
| NPM1 | AML | Increased expression of VISTA and ULBP1 (NKG2D ligand) | |
| RUNX1 | AML | High expression of B-cell–associated markers (BTN2A2, SLAMF7, and LY9) in addition to HLA II | |
| Abbas et al37 | chr7/7q loss | AML | Higher Treg and CD8+ T-cell infiltration, downregulation of IFN-γ pathway genes, and worse survival compared with AML cases with intact chr7/7q |
| Yeaton et al38 | TET2 | AML | Emergence of inflammatory monocyte-like cells during progression to myeloid transformation |
| Notarangelo et al39 | IDH1/IDH2 | Human IDH-mutant cancers | Acute but reversible inhibition of CD8+ T-cell proliferation, cytotoxicity, and IFN-γ signaling by oncometabolite d-2HG |
d-2HG, d-2-hydroxyglutarate; ICOS, inducible T-cell costimulator; MDS, myelodysplastic syndrome; TIS, tumor inflammation signature.