Investigating Anti-leukemic T Cell Response in the Bone Marrow (BM) Microenvironment
Mentor: Anastasia Tikhonova
T-cell acute lymphoblastic leukemia (T-ALL) is a particularly aggressive pediatric leukemia subtype with no targeted therapies or immune interventions. Large-scale sequencing efforts to define the genetic drivers of acute lymphoblastic leukemia at disease diagnosis and relapse have failed to inform targeted treatment strategies or predict relapse. Therefore, there is an urgent clinical need for identifying pediatric T-ALL therapeutic approaches. Targeting the immunosuppressive tumor microenvironment has revolutionized therapeutic approaches in solid tumors. High-risk leukemia such as T-ALL are thought to be resistant to targeting the exhausted tumor microenvironment due to their comparatively low mutational rate. However, comprehensive studies defining the T-ALL immune landscape has not been performed. As part of the POST program, I will leverage T-ALL animal models to functionally examine specific immune populations with the goal of redirecting the immune responses against T-ALL. Thus, I will directly compare T cell responses throughout different stages of T-ALL development and shed light on how the bone marrow (BM) microenvironment impacts leukemic disease process. Furthermore, I will assess functional changes by utilizing widely used methods in the field of hematology and pediatric oncology such as flow cytometry, BM transplantations, and in vivo T-ALL modeling. Together, this comprehensive approach will improve our understanding of the immunobiology of T-ALL and provide cellular and molecular targets for therapeutic modulation of this devastating hematologic malignancy.
