Abstract Details

Title Immuno-PET Imaging of CD69 Visualizes T-Cell Activation and Predicts Survival following Immunotherapy in Murine GBM.

Topic Neuro-oncology

Presentation(s) S17 - Innovations in Neuro-oncology (2:36 PM-2:48 PM)

Poster/Presentation
Number 009

Background Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults. Immunotherapy may be promising for the treatment of some GBM patients, however, there is a need for noninvasive neuroimaging techniques to predict immunotherapeutic responses. The effectiveness of most immunotherapeutic strategies requires T-cells activation.

Objective We aimed to evaluate an early marker of T-cell activation, CD69, for its use as an imaging biomarker of response to immunotherapy for GBM.

Design/Methods We performed CD69 immunostaining on human and mouse T-cells following in vitro activation and post-immune checkpoint inhibitors (ICI) in an orthotopic syngeneic mouse glioma model. CD69 expression on tumor-infiltrating leukocytes was assessed using single-cell RNA sequence (scRNA-seq) data from recurrent GBM patients receiving ICI. Radiolabeled CD69 antibody (Ab) positron emission tomography/computed tomography (PET/CT) imaging (CD69 immuno-PET) was performed on GBM-bearing mice longitudinally to quantify CD69 and its association with survival following immunotherapy

Results CD69 expression was upregulated upon T-cell activation and on tumor-infiltrating lymphocytes (TILs) in response to immunotherapy. Similarly, scRNA-seq data demonstrated elevated CD69 on TILs from ICI-treated recurrent GBM patients as compared with TILs from a control cohort. CD69 immuno-PET studies showed a significantly higher tracer uptake in the tumors of ICI-treated mice compared with controls. Importantly, we observed a strong positive correlation between survival and CD69 immuno-PET signals in immunotherapy-treated animals and established a trajectory of T-cell activation by virtue of CD69-immuno-PET measurements.

Conclusions Our study supports the use of CD69 immuno-PET as an early immunotherapy response assessment imaging tool for GBM patients

Authors/Disclosures
Michal Nisnboym Ziv, MD (Duke) PRESENTER	Dr. Nisnboym Ziv has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Dhivyaa Rajasundaram (University of Pittsburgh)	No disclosure on file
	No disclosure on file
Deborah T. Blumenthal, MD (Intermountain Medical Center)	Dr. Blumenthal has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Servier Affaires Medicales. Dr. Blumenthal has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novocure Israel Ltd. Dr. Blumenthal has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda Oncology. The institution of Dr. Blumenthal has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Merck Sharp and Dohme.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Frank Lieberman, MD	The institution of Dr. Lieberman has received research support from Novocure. The institution of Dr. Lieberman has received research support from Black Diamond. The institution of Dr. Lieberman has received research support from Chimerix. The institution of Dr. Lieberman has received research support from Abbvie.
Jan Drappatz, MD (University of Pittsburgh Cancer Institute)	Dr. Drappatz has stock in Pfizer. Dr. Drappatz has stock in Vertex. Dr. Drappatz has stock in GSK. The institution of Dr. Drappatz has received research support from Servier. Dr. Drappatz has received publishing royalties from a publication relating to health care.
	No disclosure on file
	No disclosure on file