American Association for Cancer Research
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Supplementary Figure 1 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

CD69 is upregulated upon T-cell activation.



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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