The Kline lab is focused on overcoming immune evasion pathways activated in blood cancers and on improving the effectiveness of immune-based treatments for people with lymphoma. Our main disease of interest is diffuse large B cell lymphoma (DLBCL), the most common type of non-Hodgkin lymphoma.
1. Characterizing features of the TME
The tumor microenvironment (TME) of DLBCL remains poorly characterized, limiting the ability to identify which patients are likely to benefit from immunotherapies. We are using novel computational methods to characterize and predict recurrent features of immune-inflamed DLBCL using multi-omic data. We are exploring how lymphoma cell-intrinsic alterations regulate the tumor microenvironment and responses to immunotherapy.
2. Improving the effectiveness of CAR T cell therapy
Chimeric antigen receptor (CAR) T cell therapy has brought significant benefits to patients with relapsed/refractory DLBCL. However, the reality remains that a majority of patients will progress. We are interested in exploring both lymphoma cell-intrinsic mechanisms of CAR T resistance and methods to improve CAR T cell persistence.
3. Enhancing anti-CD47 therapy in DLBCL
CD47 is a “don’t eat me signal” commonly expressed on lymphoma cells. When blocking the interaction of CD47 with its receptor SIRPα on macrophages, lymphoma cells are cleared. However, while the combination of anti-CD47 therapy with anti-CD20 has shown promise in the clinic, not all patients benefit from this treatment. Using a genome-wide approach, we are interested in identifying mechanisms of resistance to anti-CD47-mediated phagocytosis of lymphoma cells and candidate proteins that could be co-targeted with CD47 to improve treatment efficacy.
4. Identifying patients likely to benefit from targeted therapies
DLBCL is a heterogeneous disease. While efforts have been made to resolve this heterogeneity through transcriptional profiling and genomic clustering, identifying which DLBCLs will respond to targeted agents remains a challenge. We are working to develop novel biomarkers of response to select therapies.
5. The role of dendritic cells in anti-tumor immunity
Dendritic cells integrate environmental signals and transport antigens from peripheral tissues to lymph nodes. We are currently studying how DCs are imprinted by tumors and healthy analogous tissues at the transcriptional and epigenetic level, and how this impacts their ability to present antigens and provide costimulation to T cells.