Characteristics and clinical correlation of TIM-3 and PD-1/PD-L1 expressions in leukemic cells and tumor microenvironment in newly diagnosed acute myeloid leukemia

Abstract

Dual targeting of TIM-3 and PD-1/PD-L1 pathways is currently under investigation for cancer immunotherapy. The interaction of these immune checkpoints remains unclear in the leukemic microenvironment of acute myeloid leukemia (AML). We performed an immunophenotypic study of bone marrow in 37 newly diagnosed AML patients. High levels of TIM-3 expression on AML blasts were correlated with first 7 + 3 induction failure (CR 16.2% vs. non-CR 36.4%, p = .038). In contrast, high TIM-3 levels on natural killer (NK) cells were associated with complete remission (CR) status after induction (CR 24.7% vs. non-CR 6.5%, p = .035). Few PD-L1 positive AML blasts and PD-1 or PD-L1 positive NK cells were observed. Although the exhausted PD-1 expressing T cells were detected in 28.3% of T cells, the double positive of PD-1 and TIM-3 T cells were rarely detected. In summary, the TIM-3 levels on AML blasts and NK cells are potentially the prognostic biomarkers in AML.

Keywords:

• Acute myeloid leukemia
• T cell immunoglobulin and mucin-domain containing-3
• programmed cell death ligand 1
• programmed cell death 1
• immune checkpoint

Disclosure statement

All authors declare that they have no conflict of interest.

Additional information

Funding

This study was supported by research grants from the Ratchadapisek Sompotch Foundation [RA63/017] and the Thai Society of Hematology.