The Emerging Role of CD8⁺ T Cells in Shaping Treatment Outcomes of Patients with MDS and AML

CD8+ T cells are critical players in anti-tumor immunity against solid tumors, targeted by immunotherapies. Emerging evidence suggests that CD8+ T cells also play a crucial role in anti-tumor responses and determining treatment outcomes in hematologic malignancies like myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML). In this review, we focus on the implication of CD8+ T cells in treatment response of patients with MDS and AML. First, we review reported studies of aberrant functionality and clonality of CD8+ T cells in MDS and AML, often driven by the immunosuppressive bone marrow microenvironment, which can hinder effective antitumor immunity. Additionally, we discuss the potential use of CD8+ T cell subpopulations, including memory and senescent-like subsets, as predictive biomarkers for treatment response to a variety of treatment regimens, such as hypomethylating agents which is the standard of care for patients with higher-risk MDS, and chemotherapy which is the main treatment of patients with AML. Understanding the multifaceted role of CD8+ T cells and their interaction with malignant cells in MDS and AML, will provide useful insights into their potential as prognostic/predictive biomarkers, but also uncover alternative approaches to novel treatment strategies that could reshape the therapeutic landscape, thus improving treatment efficacy, aiding in overcoming treatment resistance and improving patient survival in these challenging myeloid neoplasms.