Immune microenvironment dysfunctions enable malignification at the onset of MDS Ganan-Gomez I, Ma F, Chien KS, Yang H, Montalban-Bravo G, Wildeman BE, Kumar B, Kim YJ, Daher M, Takahashi K, Garcia-Manero G and Colla S
4. NK Cells from CCUS Patients Are Irreversibly Dysfunctional
5. NK Cells Are Part of the Mutant CCUS Clone
Joint scDNA-seq and surface protein analysis (Tapestri)
CD8 + T
No expansion In vitro cytolysis assays with leukemic cell lines
Post-7-day NK cell expansion
CD4 + T
Young Healthy Old Healthy CCUS THP1 alone
K562 alone Young HDs Old HDs CCUS
✱✱✱✱
T Prog
✱✱✱
✱✱✱✱
✱✱✱
600
100 150 200 250
NK cells
B cells cDC pDC
400
CD16 + Mono
200
0 50
0 1020304050 0
My/Mono
0
3
6
9
12
Time (h)
Time (h)
• The innate immune repertoire is molecularly and functionally altered in patients with CCUS • Immune evasion of premalignant clones may contribute to clonal evolution to MDS • Rationale for adoptive NK cell therapy in patients with CCUS or low-burden MDS to prevent/arrest MDS progression Conclusions
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