Nicholas Ceglia
I am a principal computational biologist at Memorial Sloan Kettering Cancer Center in New York. I received a PhD in computer science from the University of California, Irvine. Currently, I lead the cellular phenotyping team under the supervision of Dr. Sohrab Shah and I am the single cell lead in the Computational Immuno-oncology initiative under the supervision of Dr. Benjamin Greenbaum. My research interest includes single cell methods and analysis of cancer evolution and the adaptive immune response.
Sessions
While immune-based therapies have transformed the treatment of many hematologic malignancies, T cell-based immunotherapies for acute myeloid leukemia (AML) have had limited success. However, the curative potential of donor T cells in allogeneic hematopoietic cell transplantation underscores the need to understand the mechanisms behind ineffective anti-leukemic T cell activity to advance these therapies. To investigate, we performed longitudinal analysis of single cell RNA-seq on pre- and serial post-treatment samples with paired CITE-seq and VDJ sequencing for 38 patients with newly diagnosed AML. These analyses reveal the immunosuppressive nature of T cells within the AML BM, the dynamic evolution of T cell clones across activation and exhaustion states, and the immunomodulatory impact of malignant AML cells on T cells. Finally, we identified key T cell intrinsic features affecting the relationship between T cell phenotype, repertoire, and disease status in the AML BM. We hypothesize that both malignant and non-malignant cells in the AML BM contribute to impaired T cell immunity, resulting in distinct T cell compositions across different disease states.