Data from Glioblastoma Vascular Plasticity Limits Effector T-cell Infiltration and Is Blocked by cAMP Activation

• DOI: 10.1158/2326-6066.c.6864860.v1
• Publication Date: 2023-10-04T07:22:00Z
• Authors: Zixi Qin; Youwei Huang; Zeying Li; Guopeng Pan; Liangying Zheng; Xiao Xiao; Fang Wang; Jiahong Chen; Xueqin Chen; Xi Lin; Kai Li; Guangmei Yan; Haipeng Zhang; Fan Xing
• Keywords: Immune checkpoint

<div>Abstract<p>Glioblastoma (GBM) is the deadliest form of brain cancer. It a highly angiogenic and immunosuppressive malignancy. Although immune checkpoint blockade therapies have revolutionized treatment for many types cancer, their therapeutic efficacy in GBM has been far less than expected or even ineffective. In this study, we found that genomic signature glioma-derived endothelial cells (GdEC) correlates with an state poor prognosis patients glioma. We established <i>in vitro</i> model GdEC differentiation drug screening used to determine cyclic adenosine monophosphate (cAMP) activators could effectively block formation by inducing oxidative stress. Furthermore, cAMP impaired vivo</i>, normalized tumor vessels, altered profile, especially increasing influx function CD8<sup>+</sup> effector T cells. Dual GdECs PD-1 induced regression antitumor memory. Thus, our study reveals transdifferentiation shapes cell barrier supports clinical development combining immunotherapy GBM.</p><p><i><a href="https://aacrjournals.org/cancerimmunolres/article/doi/10.1158/2326-6066.CIR-23-0667" target="_blank">See related Spotlight Lee et al., p. 1300</a></i></p></div>