T cell exhaustion: Supremacy in leukemia as for disease and therapy

Document Type : Review Article

Authors

1 Department of Microbiology and Immunology, Faculty of Pharmacy, Sphinx University, Assiut, Egypt.

2 Department of Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt

3 Department of Microbiology and Immunology, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.

4 Department of clinical pathology, South Egypt cancer Institute, Assiut, University, Assiut 71515, Egypt.

5 Department of Microbiology and Immunology, Faculty of Pharmacy, Minia University, Minia 61519, Egypt

Abstract

In this review, an overview of exhausted T cells in acute and chronic leukemias including myelocytic and lymphoblastic leukemia was made to browse this important subset of cells and highlight circumstantial phenotypic, genotypic, and transcriptional alterations. Ultimately, these changes affect the development and progression of the disease. The process of T cell dysfunction and exhaustion in leukemia is briefly described with special emphasis on the phenotypic state of T cells together with immune checkpoints (ICs) which are frequently altered in this setting. New immune therapeutic approaches are being developed for the treatment of the disease; including IC blockers which are especially designed to block molecular targets specific to leukemia. Furthermore, the interaction of exhausted T cells subset with these therapeutic approaches especially T-cell-based therapeutic strategies such as T cell receptor (TCR)- engineered lymphocytes; and chimeric antigen receptors (CARs) is discussed. This accordingly will improve our understanding of the resistance to therapy and thus may improve our therapeutic strategies.

Keywords