Immune microenvironment

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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