Zhewen (Kevin) Li - Graduate Student

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy driven by somatic mutations in hematopoietic stem and progenitor cells, resulting in uncontrolled myeloid proliferation and impaired normal hematopoiesis. Despite advances in treatment, curing AML remains challenging, as allogeneic hematopoietic stem cell transplantation—where donor T cells recognize AML cells as “non-self” target—remains the only therapy with curative potential. Notably, AML cells actively remodel the bone marrow microenvironment (BMME) by suppressing immune function and promoting immune evasion, which may explain the limited efficacy of immunotherapies such as immune checkpoint blockade and CAR-T cell therapy in AML.

CD8⁺ T cells are among the most potent cytotoxic lymphocytes capable of eliminating malignant cells; however, the mechanisms by which AML escapes CD8⁺ T cell–mediated killing remain poorly understood. In this study, we aim to characterize CD8⁺ T cell phenotypes in advanced AML, defined by approximately 50% leukemic burden in the bone marrow, and to identify potential targets to restore CD8⁺ T cell function. Based on clinical observations, we hypothesized that CD8⁺ T cells become exhausted and dysfunctional within the AML BMME. Using flow cytometry, we found that CD8⁺ T cells from AML-bearing mice exhibit persistent expression of TOX, a key transcriptional regulator of T cell exhaustion, along with increased expression of inhibitory and dysfunction-associated receptors including PD-1, TIM-3, and KLRG-1. These results suggest potential exhaustion phenotypes. To further define the transcriptional and functional states of these cells and to uncover therapeutic vulnerabilities, we plan to integrate single-cell RNA sequencing with functional assays. Together, this work aims to advance our understanding of CD8⁺ T cell dysfunction in AML and inform strategies to reinvigorate anti-leukemic immunity.

 Jan 29, 2026 @ 12:00 p.m.
 Medical Center | K307 (3-6408)