American Association for Cancer Research
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Supplementary Figure 10 from Immuno-PET Imaging of CD69 Visualizes T-Cell Activation and Predicts Survival following Immunotherapy in Murine GBM.

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posted on 2023-06-09, 13:00 authored by Michal Nisnboym, Sarah R. Vincze, Zujian Xiong, Chaim T. Sneiderman, Rebecca A. Raphael, Bo Li, ReidAnn E. Sever, Ambika P. Jaswal, Kathryn E. Day, Joseph D Latoche, Lesley M Foley, Hanieh Karimi, T. Kevin Hitchens, Sameer Agnihotri, Baoli Hu, Dhivyaa Rajasundaram, Carolyn J Anderson, Deborah T. Blumenthal, Thomas M. Pearce, Shikhar Uttam, Jessie R. Nedrow, Ashok Panigrahy, Ian F Pollack, Frank S Lieberman, Jan Drappatz, Itay Raphael, Wilson B. Edwards, Gary Kohanbash

MRI analysis of tumor volume before and after treatment.



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 non-invasive neuroimaging techniques to predict immunotherapeutic responses. The effectiveness of most immunotherapeutic strategies requires T-cells activation. Therefore, 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. Herein, 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. We show CD69 expression is 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 control cohorts. CD69 immuno-PET studies showed a significantly higher tracer uptake in the tumors of ICI-treated mice compared with controls. Importantly, we observed a 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. Our study supports the potential use of CD69 immuno-PET as an immunotherapy response assessment imaging tool for GBM patients.

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