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On-Demand e-Posters Display

188P - TIM-3 expression and markers of immune escape on leukemia cells

Date

09 Dec 2021

Session

On-Demand e-Posters Display

Presenters

Katerina Kuzelova

Citation

Annals of Oncology (2021) 32 (suppl_7): S1458-S1464. 10.1016/annonc/annonc788

Authors

K. Kuzelova, B. Brodská, P. Otevrelova, C. Salek

Author affiliations

  • Institute of Hematology and Blood Transfusion, 128 20 - Prague/CZ
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Abstract 188P

Background

TIM-3 is a known marker of T-cell exhaustion but it is also commonly found on leukemia blasts in acute myeloid leukemia (AML). TIM-3 positivity of AML blasts was associated with higher relapse rate and worse overall survival. Although TIM-3 function in AML cells is far from elucidated, TIM-3 was reported to mediate Galectin-9 secretion, and TIM-3/Galectin-9 release in the plasma might contribute to inhibition of T-cell effector function.

Methods

Transcript and surface protein levels of TIM-3 were analyzed in 53 samples of primary AML cells obtained from leukapheresis at diagnosis. In parallel, we measured surface expression of PD-L1 and the invariant peptide CLIP as a marker of lowered antigen presentation. TIM-3 transcript was also analyzed in an independent larger cohort obtained from Vizome/BeatAML database.

Results

The fraction of leukemia cells with surface TIM-3 expression correlated with TIM-3 transcript levels (p less than 0.0001). TIM-3 amount on leukemia cells positively correlated with surface PD-L1 expression (p = 0.0034) and CLIP (p = 0.0012). Consistently with previous reports, high TIM-3 expression was associated with worse overall survival (p = 0.001). The group of patients with very low levels of TIM-3/PD-L1/CLIP included in particular many cases with nucleophosmin 1 (NPM1) mutation (14 of 16), which is a known favorable prognostic factor in AML. Analysis of the independent cohort from Vizome/BeatAML (N = 448) confirmed significantly lower levels of TIM-3 transcript in patients with NPM1 mutation compared to those with wild-type NPM1 (p = 0.013).

Conclusions

Our results show that the prognostic impact of TIM-3 expression on AML blasts might be related to parallel activation of immune escape mechanisms, such as expression of the inhibitory PD-L1 receptor or decreased antigen presentation.

Legal entity responsible for the study

The authors.

Funding

Czech Science Foundation (grant No. 19-04099S); Ministry of Health, Czech Republic (project for conceptual development of the research organization No 00023736).

Disclosure

All authors have declared no conflicts of interest.

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