While advances in the treatment of acute lymphoblastic leukemia (ALL) have improved survival rates, it remains the most common pediatric cancer and the most common cause of death due to cancer in patients under 20. Morbidity and mortality are driven in part by infiltration of the central nervous system (CNS), and current treatments for ALL that has spread to the CNS are associated with neurotoxicity and cognitive decline.
For this project, Susan Schwab is using mouse models to study how a subset of ALL derived from the T cell lineage (T-ALL) infiltrates the CNS. Dr. Schwab’s team has found that the loss of two integrins commonly required for normal T cell infiltration of the CNS paradoxically increase T-ALL infiltration of the CNS. They are examining how the loss of these integrins promotes CNS migration and how native immune cells in the CNS respond to these cancer cells and their integrins. They are also studying how additional factors may allow T-ALL to proliferate in the CNS. These studies will deepen our understanding of leukemic spread to the CNS and identify weak points for more effective and less toxic therapies.
PUBLISHED RESEARCH
Baeyens A, Bracero S, Chaluvadi VS, Khodadadi-Jamayran A, Cammer M, Schwab SR. Monocyte-derived S1P in the lymph node regulates immune responses. Nature. 2021.
Okuniewska M, Fang V, Baeyens A, Raghavan V, Lee JY, Littman DR, Schwab SR. SPNS2 enables T cell egress from lymph nodes during an immune response. Cell Rep. 2021.
Dixit D, Hallisey VM, Zhu EY, Okuniewska M, Cadwell K, Chipuk JE, Axelrad JE, Schwab SR. S1PR1 inhibition induces proapoptotic signaling in T cells and limits humoral responses within lymph nodes. J Clin Invest. 2024.