Profiling of CD8+ Cytotoxic T Lymphocytes to Identify Optimal Hematopoietic Stem Cell Transplantation Approach in B-cell Acute Lymphoblastic Leukemia

B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric blood cancer. Despite advances in treatment therapies, the disease remains a clinical challenge due to high relapse rates and poor immune responses. Hematopoietic stem cell transplantation (HSCT) offers a potential cure through graft-versus-leukemia effects, but outcomes vary among different transplantation approaches. In this critical review of existing research and proposed project, I will investigate varied treatment outcomes across three types of HSCT approaches through comprehensively profiling CD8+ T-cell phenotype, transcriptional profiles, and functional capacity, to understand the cellular and molecular mechanisms. Using flow cytometry, proliferation assays, single-cell RNA sequencing, T-cell receptor clonotype analysis, and xenograft mouse models engrafted with B-ALL cells in vivo, I will characterize CD8+ T-cell reconstitution and identify immune features that associate with transplant effectiveness. By comparing the functional characteristics of CD8+ T cells across different transplant approaches, this proposal will not only help identify the most effective type of HSCT, but also provides deeper understanding into the factors affecting post-transplant prognosis. In the long term, this approach will provide phenotypic reference to evaluate and optimize current HSCT therapies.