A T-cell receptor as a promising immunotherapeutic target in acute myeloid leukemia: expression of T cell immunoglobulin and mucin-containing-3 on bone marrow hematopoietic cells

Abstract

Background The emergence of immunotherapy has changed the treatment landscape of various types of cancers. However, limited target antigen remains to be a challenge for its application in acute myeloid leukemia (AML). T cell immunoglobulin and mucin-containing-3 (Tim-3) is an immune checkpoint receptor that plays a major role in the escape of host immune surveillance in AML. Thus, its role in cancer treatment needs to be thoroughly investigated. Methods Tim-3 expression on blasts, lymphocytes, and monocytes was analyzed by flow cytometry in bone marrow samples of 60 newly diagnosed AML patients and 30 matched non-neoplastic controls. Its association with different prognostic clinicopathological parameters was also evaluated. ROC curve confirmed the value of Tim-3 expression in discriminating AML patients from healthy controls and the role of Tim-3 in disease aggressiveness was also investigated. Results The median percentage of myeloblasts positive for Tim-3% and MFI were significantly higher in AML than normal controls (64.27% and 1.34 in patients vs. 41.89% and 1.12 in controls) and it was markedly associated with poor overall survival of the patients. Besides, the upregulation of Tim-3 on AML blasts was significantly higher than on lymphocytes and monocytes in denovo AML patients ( P <0.001). Conclusion This study indicates Tim-3 as a poor prognostic marker in AML and highlights Tim-3 as a new therapeutic target antigen for immunotherapy with low off-target toxicity.