School of Biomedical Sciences cordially invites you to join the following seminar and career talk:

Speaker: Dr. Rongze "Olivia" Lu, Associate Professor of Neurological Surgery and Brain Tumor Center, University of California San Francisco
Host: Professor Rio Sugimura

Seminar

Talk Title: Novel therapeutic targets in tumor associated myeloid cells
Date: 7 March 2024 (Thursday)
Time: 10:00 am – 11:00 am
Venue: Lecture Theatre 1, G/F, William M.W. Mong Block, 21 Sassoon Road
*Prior Registration is not required to attend this seminar

Career Talk

Date: 7 March 2024 (Thursday)
Time: 11:00 am – 12:00 nn
Venue: Lecture Theatre 1, G/F, William M.W. Mong Block, 21 Sassoon Road
Sign-up: https://hku.au1.qualtrics.com/jfe/form/SV_9TxVIDikSyAdgEK

Biography
Dr. Rongze “Olivia” Lu is an Associate Professor of Neurological Surgery and Brain Tumor Center at UCSF. Her lab is focused on investigating the molecular mechanisms of immune suppression and evasion in brain tumor microenvironment with the goal to develop novel immunotherapeutic for brain tumor. Dr. Lu’s previous research has identified that protein phosphatase 2A (PP2A) regulates immune suppression and evasion in cancer cells, macrophages and T cells in multiple tumor models. Based on those findings, a Phase I/II trial (NCT03027388) of PP2A inhibitor in recurrent glioblastoma and Phase I/II( NCT06065462) of PP2A inhibitor combined with PD-1 antibody for ovarian cancer were initiated.

Dr. Lu received her Ph.D in Cancer Immunology from Beckman Research Institute at City of Hope. She then pursued post doctorate studies at Genentech. Olivia serves on the Early Career Scientist Committee since 2020 and has organized grant writing workshop for SITC annual meeting since 2020. She has received Career Development Award for Peer Reviewed Cancer Research Program from Department of Defense, Early Career Investigator Award from Keystone conference, NIH SPORE award and a RO1 award to study the role of STING-Type I IFN signaling in glioma associated macrophage/microglia.

Abstract
Stimulator of IFN genes type I (STING-Type I) IFN signaling in myeloid cells plays a critical role in effective antitumor immune responses, but STING agonists as monotherapy have shown limited efficacy in clinical trials. The mechanisms that downregulate STING signaling are not fully understood. Here, we report that protein phosphatase 2A (PP2A), with its specific B regulatory subunit Striatin 4 (STRN4), negatively regulated STING-Type I IFN in macrophages. Mice with macrophage PP2A deficiency exhibited reduced tumor progression. The tumor microenvironment showed decreased immunosuppressive and increased IFN-activated macrophages and CD8⁺ T cells. Mechanistically, we demonstrated that Hippo kinase MST1/2 was required for STING activation. STING agonists induced dissociation of PP2A from MST1/2 in normal macrophages, but not in tumor conditioned macrophages. Furthermore, our data showed that STRN4 mediated PP2A binding to and dephosphorylation of Hippo kinase MST1/2, resulting in stabilization of YAP/TAZ to antagonize STING activation. In human patients with glioblastoma (GBM), YAP/TAZ was highly expressed in tumor-associated macrophages but not in nontumor macrophages. We also demonstrated that PP2A/STRN4 deficiency in macrophages reduced YAP/TAZ expression and sensitized tumor-conditioned macrophages to STING stimulation. In summary, we demonstrated that PP2A/STRN4-YAP/TAZ has, in our opinion, been an unappreciated mechanism that mediates immunosuppression in tumor-associated macrophages, and targeting the PP2A/STRN4-YAP/TAZ axis can sensitize tumors to immunotherapy.

ALL ARE WELCOME

Should you have any enquiries, please feel free to contact Miss Angela Wong at 3917 9216.