We leverage patient-derived 3D organoid models from different cancers, which reproduce the oncogenic programs of human tumors, to reveal cellular and molecular mechanisms underlying tumor-intrinsic sensitivity to IFNg. The talk will address:

• How intratumoral genetic heterogeneity influences sensitivity to IFNg signaling.
• How intratumoral genetic heterogeneity influences the expression of IFNg-induced and therapeutically relevant immune checkpoints and soluble mediators. Such insights are key to the development of combination treatments targeting immune checkpoint ligands and tumor-specific vulnerabilities.
• Given the critical role of IFNg in antitumor immunity, we address how tissue-specific and tumor-intrinsic differences must be considered to identify targetable immunophenotypes and underlying molecular cascades that influence IFNg responsivity and ICB efficacy.

About Dr. Anna S. Tocheva:
My laboratory integrates cellular and molecular immunological assays with high-throughput proteomic and genomic approaches to study the signaling pathways triggered by immune checkpoints in human T cells. In parallel, we develop scalable approaches that incorporate cancer patient-derived organoids with reconstituted immune cells allowing us to translate these fundamental immunobiology discoveries into functional pre-clinical immunoassays to identify mono- and combination immunotherapies that augment anti-tumor T cell responses.

— Anna S. Tocheva, Ph.D.
Assistant Professor
Department of Genetics and Genomic Sciences
Icahn School of Medicine at Mount Sinai