Program: Oral and Poster Abstracts
Session: 622. Lymphomas: Translational – Non-Genetic: Poster I
Hematology Disease Topics & Pathways:
ALL, Research, Lymphoid Leukemias, Translational Research, Lymphomas, Bioinformatics, T Cell lymphoma, Immune mechanism, Diseases, Immunology, Lymphoid Malignancies, Biological Processes, Technology and Procedures, Study Population, Profiling, Animal model
Session: 622. Lymphomas: Translational – Non-Genetic: Poster I
Hematology Disease Topics & Pathways:
ALL, Research, Lymphoid Leukemias, Translational Research, Lymphomas, Bioinformatics, T Cell lymphoma, Immune mechanism, Diseases, Immunology, Lymphoid Malignancies, Biological Processes, Technology and Procedures, Study Population, Profiling, Animal model
Saturday, December 7, 2024, 5:30 PM-7:30 PM
The MYC oncogene is activated and a driving factor in the pathogenesis of many hematopoietic cancers including T-cell acute lymphoblastic leukemia/lymphoma (T-ALL). Previously, our group showed that MYC suppresses the immune system and that MYC inhibition in cancer cells can restore normal immune surveillance mechanisms through the activation of CD4+ T-cells, NK cells and innate immune responses and identified a role for Type I interferons. Now, we have performed a time-course in vivo analysis of changes in the immune system before and after experimental MYC inactivation in a transgenic mouse conditional model of MYC-driven T-ALL. Using multi-parameter flow-cytometry analysis of immune cells, we found that upon MYC activation (MYC ON) and the initiation of tumorigenesis, and upon MYC inactivation and tumor regression, there is a unique pattern of changes in CD4+ T-cells, Natural Killer cells and antigen presenting cells (APC). Specifically, we identified the expansion of immature double positive T-cells and contraction of CD4+ T-cells and NK cells in MYC ON mice with re-establishment of normal proportions of these subsets after MYC inactivation. Interestingly, in MYC ON mice, the overall frequency of MHC II positive APC was unchanged. However, there were dynamic shifts within MHC class II positive subsets associated with MYC activation including a reduction in the proportions of CD11b+Ly6C+ monocytes and F4/80+ macrophages, which were restored to normal by MYC inactivation. Finally, in MYC ON mice, we observed that splenic B-cells had increased MHC II expression that reverted to baseline following MYC inactivation. MYC ON mice additionally exhibited expansion of plasmacytoid and CD8alpha negative dendritic cells that normalized with MYC inhibition. Analysis of human T-ALL transcriptomic data further identified that MYC influences immune surveillance. Together, our results suggest that MYC may promote the development of T-ALL by altering antigen presenting cells within the tumor microenvironment possibly contributing to immune exhaustion. Inactivation of MYC thus has the potential to re-establish critical immune regulatory mechanisms.
Disclosures: No relevant conflicts of interest to declare.
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