09-11, 11:45–12:00 (Europe/Berlin), Main conference room - MW 0350
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.
Using a growing clinically annotated sample set of over 79 viably preserved BM aspirates from 38 patients with newly diagnosed AML, we have developed an scverse-based analysis workflow to perform classification of T cell phenotypes, track phenotypic evolution of T cell clones across pre- and serial post-treatment samples, understand the dependence of phenotype and clonotype across different disease states including remission and progressive disease, and identify changing immunoregulatory surface proteins and transcriptional programs on both malignant and non-malignant cells. Alongside several in-house methods (genevector and TCRi), these analyses are performed using both Scanpy and Scirpy packages.
No previous knowledge expected
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.