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Citations to this article

STING agonist 8803 reprograms the immune microenvironment and increases survival in preclinical models of glioblastoma
Hinda Najem, … , Michael A. Curran, Amy B. Heimberger
Hinda Najem, … , Michael A. Curran, Amy B. Heimberger
Published June 17, 2024
Citation Information: J Clin Invest. 2024;134(12):e175033. https://doi.org/10.1172/JCI175033.
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Research Article Immunology Oncology Article has an altmetric score of 30

STING agonist 8803 reprograms the immune microenvironment and increases survival in preclinical models of glioblastoma

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Abstract

STING agonists can reprogram the tumor microenvironment to induce immunological clearance within the central nervous system. Using multiplexed sequential immunofluorescence (SeqIF) and the Ivy Glioblastoma Atlas, STING expression was found in myeloid populations and in the perivascular space. The STING agonist 8803 increased median survival in multiple preclinical models of glioblastoma, including QPP8, an immune checkpoint blockade–resistant model, where 100% of mice were cured. Ex vivo flow cytometry profiling during the therapeutic window demonstrated increases in myeloid tumor trafficking and activation, alongside enhancement of CD8+ T cell and NK effector responses. Treatment with 8803 reprogrammed microglia to express costimulatory CD80/CD86 and iNOS, while decreasing immunosuppressive CD206 and arginase. In humanized mice, where tumor cell STING is epigenetically silenced, 8803 therapeutic activity was maintained, further attesting to myeloid dependency and reprogramming. Although the combination with a STAT3 inhibitor did not further enhance STING agonist activity, the addition of anti–PD-1 antibodies to 8803 treatment enhanced survival in an immune checkpoint blockade–responsive glioma model. In summary, 8803 as a monotherapy demonstrates marked in vivo therapeutic activity, meriting consideration for clinical translation.

Authors

Hinda Najem, Spencer T. Lea, Shashwat Tripathi, Lisa Hurley, Chao-Hsien Chen, Ivana William, Moloud Sooreshjani, Michelle Bowie, Genevieve Hartley, Corey Dussold, Sebastian Pacheco, Crismita Dmello, Catalina Lee-Chang, Kathleen McCortney, Alicia Steffens, Jordain Walshon, Martina Ott, Jun Wei, Anantha Marisetty, Irina Balyasnikova, Roger Stupp, Rimas V. Lukas, Jian Hu, Charles David James, Craig M. Horbinski, Maciej S. Lesniak, David M. Ashley, Waldemar Priebe, Leonidas C. Platanias, Michael A. Curran, Amy B. Heimberger

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Total citations by year

Year: 2025 2024 Total
Citations: 6 4 10
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2024 (4)

Title and authors Publication Year
2024 Lasker Award Recipient Zhijian Chen elucidates how DNA stimulates immunity
Heimberger AB
The Journal of Clinical Investigation 2024
Immunotherapy for glioblastoma: current state, challenges, and future perspectives.
Liu Y, Zhou F, Ali H, Lathia JD, Chen P
Cellular & molecular immunology 2024
Unveiling the significance of cancer-testis antigens and their implications for immunotherapy in glioma
Zhuo S, Yang S, Chen S, Ding Y, Cheng H, Yang L, Wang K, Yang K
Discover Oncology 2024
Immune Checkpoint Inhibitors in Glioblastoma IDHwt Treatment: A Systematic Review
Baskaran AB, Kozel OA, Venkatesh O, Wainwright DA, Sonabend AM, Heimberger AB, Lukas RV
Cancers 2024

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Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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