The expression profile and tumorigenic mechanisms of CD97 (ADGRE5) in glioblastoma render it a targetable vulnerability

Ravn-Boess, Niklas; Roy, Nainita; Hattori, Takamitsu; Bready, Devin; Donaldson, Hayley; Lawson, Christopher; Lapierre, Cathryn; Korman, Aryeh; Rodrick, Tori; Liu, Enze; Frenster, Joshua D.; Stephan, Gabriele; Wilcox, Jordan; Corrado, Alexis D.; Cai, Julia; Ronnen, Rebecca; Wang, Shuai; Haddock, Sara; Sabio Ortiz, Jonathan; Mishkit, Orin; Khodadadi-Jamayran, Alireza; Tsirigos, Aris; Fenyö, David; Zagzag, David; Drube, Julia; Hoffmann, Carsten; Perna, Fabiana; Jones, Drew R.; Possemato, Richard; Koide, Akiko; Koide, Shohei; Park, Christopher Y.; Placantonakis, Dimitris G.

doi:10.1016/j.celrep.2023.113374

Cited by 6 publications

(3 citation statements)

References 101 publications

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“…indicate that CEACAM5 overexpression can promote tumour growth through the EMT pathway in the localized regions of aggressive cancer 43 . ADGRE5 (CD97) has been considered as the most promising target of adhesion G protein‐coupled receptors in glioblastoma 44 . ADGRE5 in retinal pigment epithelial cells also controls leukocyte activation and trafficking in uveal retinal inflammation 45 .…”

Section: Discussionmentioning

confidence: 99%

“… 43 ADGRE5 (CD97) has been considered as the most promising target of adhesion G protein‐coupled receptors in glioblastoma. 44 ADGRE5 in retinal pigment epithelial cells also controls leukocyte activation and trafficking in uveal retinal inflammation. 45 CD55, a complement regulatory protein, binds to multiple ligands that are constitutively expressed on monocytes or granulocytes and is rapidly upregulated during activation of T cells.…”

Section: Discussionmentioning

confidence: 99%

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Single‐cell analysis revealed a potential role of T‐cell exhaustion in colorectal cancer with liver metastasis

Ling,

Zhang,

Liu

et al. 2024

J Cellular Molecular Medi

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Liver metastasis (LM) is an important factor leading to colorectal cancer (CRC) mortality. However, the effect of T‐cell exhaustion on LM in CRC is unclear. Single‐cell sequencing data derived from the Gene Expression Omnibus database. Data were normalized using the Seurat package and subsequently clustered and annotated into different cell clusters. The differentiation trajectories of epithelial cells and T cells were characterized based on pseudo‐time analysis. Single‐sample gene set enrichment analysis (ssGSEA) was used to calculate enrichment scores for different cell clusters and to identify enriched biological pathways. Finally, cell communication analysis was performed. Nine cell subpopulations were identified from CRC samples with LM. The proportion of T cells increased in LM. T cells can be subdivided into NK/T cells, regulatory T cells (Treg) and exhausted T cells (Tex). In LM, cell adhesion and proliferation activity of Tex were promoted. Epithelial cells can be categorized into six subpopulations. The transformation of primary CRC into LM involved two evolutionary branches of Tex cells. Epithelial cells two were at the beginning of the trajectory in CRC but at the end of the trajectory in CRC with LM. The receptor ligands CEACAM5 and ADGRE5‐CD55 played critical roles in the interactions between Tex and Treg cell‐epithelial cell, which may promote the epithelial‐mesenchymal transition process in CRC. Tex cells are able to promote the process of LM in CRC, which in turn promotes tumour development. This provides a new perspective on the treatment and diagnosis of CRC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Single‐cell analysis revealed a potential role of T‐cell exhaustion in colorectal cancer with liver metastasis

Ling,

Zhang,

Liu

et al. 2024

J Cellular Molecular Medi

View full text Add to dashboard Cite

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“…CD97 is associated with cell proliferation, brain invasion, and tumor metabolism in GBM [ 696 ]. It promotes Warburg metabolism through signaling mechanisms, including receptor cytoplasmic C-terminal phosphorylation, β-arrestin recruitment, and activating MAPK/ERK signal, thereby contributing to tumorigenesis in GBM [ 697 ]. The ADC targeting CD97 has demonstrated selective killing of patient-derived GBM cultures while sparing neural stem cells and non-neoplastic human astrocytes.…”

Section: Current Treatment Strategies and Progress Of Glioblastomamentioning

confidence: 99%

Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives

Lin,

Liu,

et al. 2024

J Hematol Oncol

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Glioblastoma (GBM), the predominant and primary malignant intracranial tumor, poses a formidable challenge due to its immunosuppressive microenvironment, thereby confounding conventional therapeutic interventions. Despite the established treatment regimen comprising surgical intervention, radiotherapy, temozolomide administration, and the exploration of emerging modalities such as immunotherapy and integration of medicine and engineering technology therapy, the efficacy of these approaches remains constrained, resulting in suboptimal prognostic outcomes. In recent years, intensive scrutiny of the inhibitory and immunosuppressive milieu within GBM has underscored the significance of cellular constituents of the GBM microenvironment and their interactions with malignant cells and neurons. Novel immune and targeted therapy strategies have emerged, offering promising avenues for advancing GBM treatment. One pivotal mechanism orchestrating immunosuppression in GBM involves the aggregation of myeloid-derived suppressor cells (MDSCs), glioma-associated macrophage/microglia (GAM), and regulatory T cells (Tregs). Among these, MDSCs, though constituting a minority (4–8%) of CD45+ cells in GBM, play a central component in fostering immune evasion and propelling tumor progression, angiogenesis, invasion, and metastasis. MDSCs deploy intricate immunosuppressive mechanisms that adapt to the dynamic tumor microenvironment (TME). Understanding the interplay between GBM and MDSCs provides a compelling basis for therapeutic interventions. This review seeks to elucidate the immune regulatory mechanisms inherent in the GBM microenvironment, explore existing therapeutic targets, and consolidate recent insights into MDSC induction and their contribution to GBM immunosuppression. Additionally, the review comprehensively surveys ongoing clinical trials and potential treatment strategies, envisioning a future where targeting MDSCs could reshape the immune landscape of GBM. Through the synergistic integration of immunotherapy with other therapeutic modalities, this approach can establish a multidisciplinary, multi-target paradigm, ultimately improving the prognosis and quality of life in patients with GBM.

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CD97 maintains tumorigenicity of glioblastoma stem cells via mTORC2 signaling and is targeted by CAR Th9 cells

Zhou,

Lin,

Jin

et al. 2024

Cell Reports Medicine

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The expression profile and tumorigenic mechanisms of CD97 (ADGRE5) in glioblastoma render it a targetable vulnerability

Cited by 6 publications

References 101 publications

Single‐cell analysis revealed a potential role of T‐cell exhaustion in colorectal cancer with liver metastasis

Single‐cell analysis revealed a potential role of T‐cell exhaustion in colorectal cancer with liver metastasis

Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives

CD97 maintains tumorigenicity of glioblastoma stem cells via mTORC2 signaling and is targeted by CAR Th9 cells

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