Plasmacytoid Dendritic Cells, an Unexplored Antigen-Presenting Myeloid Cell Type in Glioblastoma

Sunday, May 5, 2024

1:51 PM – 1:53 PM CT

Location: S405a

Presenting Author(s)

Janet Y. Wu, BA, BM

Medical Student
Stanford University School of Medicine

Co-Author(s)

KC

Kwang Bog Cho, PhD

Postdoctoral Scholar
Stanford University School of Medicine, United States
JC

John Choi, MD

Neurosurgery Resident
Stanford University School of Medicine
Stanford, California, United States
SL

Si Yeon Lee, BS

Life Science Research Professional
Stanford University School of Medicine, United States
Gordon Li, MD

Professor of Neurosurgery
Stanford University School of Medicine
Stanford, California, United States
Michael Lim, MD

Professor and Chair of Neurosurgery
Stanford University School of Medicine
Stanford, California, United States
RN

Ryan Nitta, PhD

Senior Research Scientist
Stanford University School of Medicine, United States
AR

Alexander Ren, MPhil

Medical Student
Stanford University School of Medicine, United States
CW

Caren Y. Wu, PhD

Postdoctoral Scholar
Stanford University School of Medicine, United States

Disclosure(s):

Janet Y. Wu, BA, BM: No financial relationships to disclose

Michael Lim, MD: Egret Therapeutics: Ownership or Partnership (Ongoing)

Introduction: Myeloid cell activation in the tumor microenvironment (TME) is poorly defined in glioblastoma (GBM). Stimulator of Interferon Genes (STING) is thought to be a general myeloid cell reactivator, yet it is unclear how STING can activate myeloid cells in glioblastoma (GBM). Our aim is to reverse myelosuppression via antigen presentation and increased trafficking to the TME: here we investigate the impact of local STING delivery on dendritic cell (DC) antigen presentation and on immune cell trafficking to the TME, the brain, and tumor draining lymph nodes.

Methods: Mice orthotopically implanted with GL261-luciferase glioma cells were intracranially injected with 1ug STING (2’,3’-cGAMP) 10 days after tumor implantation. Ex vivo flow cytometry for CD11b, CD11c, CD103, Ly-6C, and CD45R/B220 were used to analyze DC subpopulations while CD3 and CD69 were used to assess T cell activation. DQ-ovalbumin assays 24 hours pre-harvest for flow cytometry were used to assess antigen presentation. Kaplan-Meier curves were generated to assess the impact of STING on overall survival (OS).

Results: Mice treated with intracranial STING demonstrated enhanced recruitment of CD11c+ DCs in both the brain and deep cervical (draining) lymph nodes. This was also associated with increased antigen-presentation ability, as shown by DQ-ovalbumin signaling in these lymph nodes via conventional DCs type 1 and plasmacytoid DCs (pDCs). Intracranial STING treated mice also showed significantly increased OS when compared to sham-treated mice.

Conclusion : Our findings identify and highlight an active pDC population in the brain and tumor-draining lymph nodes that has previously not been explored in the GBM literature. These cells process and present antigens in the draining lymph nodes, proliferate and traffic to the brain, and activate T cells in the TME. Given enhanced OS, these findings provide rationale for activating antigen presentation in these DC populations to allow for an antitumor immune response.