Föreläsningar och seminarier CCK-föreläsning: Epigenetic Modulation Drives Inflammatory Responses in Sarcoma
Talare: Andreas Lundqvist, Dept of Oncology-Pathology, Karolinska Institutet
Host: Tara Hessa and Ingemar Ernberg, CCK
Insufficient T cell infiltration limits immunotherapy effectiveness in sarcoma, yet the tumor intrinsic mechanisms driving immune exclusion remain unclear. We identify H3K27ac as a key regulator of CD8⁺ T cell infiltration, with entinostat mediated elevation of this mark enhancing T cell activation, cytotoxicity, and TRM recruitment. These effects arise from a Hippo pathway switch in which YAP1 is suppressed and VGLL3 is induced, shifting transcription toward an immune responsive state. VGLL3/CD103 signatures predict anti-PD 1 responsiveness. Combining H3K27ac induction with PD 1 blockade boosts T cell–mediated killing, supporting epigenetic preconditioning as a strategy to improve sarcoma immunotherapy.
Andreas Lundqvist is professor at and deputy chair of Department of Oncology-Pathology. After his PhD at KI in 1993 he did a post doc at the National Institutes of Health and was subsequenty a research fellow 2003 -2008.
His research focuses on understanding how the immune system is regulated in patients with cancer. With this knowledge we aim to develop improved immunotherapies in patients with cancer.