Overexpression of CD99 is associated with tumor adaptiveness and indicates the tumor recurrence and therapeutic responses in gliomas

Shang, Erfei; Sun, Shanyue; Zhang, Ruolan; Cao, Zehui; Chen, Qingwang; Shi, Leming; Wu, Jinsong; Liu, Yingchao; Zheng, Yuanting

doi:10.1016/j.tranon.2023.101759

Cited by 6 publications

(10 citation statements)

References 57 publications

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“…The homophilic CD99-CD99 interaction was demonstrated by most TAMs in our analyses. Previous studies show CD99 ligation presents an apoptotic feature in developing T lymphocytes, with increased CD99 expression associated with immune adaptation dominated by TAMs in gliomas 58 . The TAMs also interacted with lymphocytes through expression of CD86, which acts as the dominant ligand for CD4 + FoxP3 + regulatory T cell survival and proliferation, interacting with CD28 and CTLA4 receptors on the regulatory T cells 59 .…”

Section: Discussionmentioning

confidence: 87%

Single-cell analysis reveals diversity of tumor-associated macrophages and their interactions with T lymphocytes in glioblastoma

Batchu,

Hanafy,

Redjal

et al. 2023

Sci Rep

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Glioblastoma (GBM) is an aggressive primary CNS malignancy and clinical outcomes have remained stagnant despite introduction of new treatments. Understanding the tumor microenvironment (TME) in which tumor associated macrophages (TAMs) interact with T cells has been of great interest. Although previous studies examining TAMs in GBM have shown that certain TAMs are associated with specific clinical and/or pathologic features, these studies used an outdated M1/M2 paradigm of macrophage polarization and failed to include the continuum of TAM states in GBM. Perhaps most significantly, the interactions of TAMs with T cells have yet to be fully explored. Our study uses single-cell RNA sequencing data from adult IDH-wildtype GBM, with the primary aim of deciphering the cellular interactions of the 7 TAM subtypes with T cells in the GBM TME. Furthermore, the interactions discovered herein are compared to IDH-mutant astrocytoma, allowing for focus on the cellular ecosystem unique to GBM. The resulting ligand-receptor interactions, signaling sources, and global communication patterns discovered provide a framework for future studies to explore methods of leveraging the immune system for treating GBM.

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Section: Discussionmentioning

confidence: 87%

Single-cell analysis reveals diversity of tumor-associated macrophages and their interactions with T lymphocytes in glioblastoma

Batchu,

Hanafy,

Redjal

et al. 2023

Sci Rep

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“…CD99 dysregulation has been observed in various cancers, and the signalling it mediates is significantly associated with tumour cell migration, invasion, metastasis and immune regulation 49,50 . In glioblastoma, high CD99 expression has been found to promote tumour cell migration, invasion and the formation of an immune‐suppressive microenvironment 51,52 . Overactive activation of the EGF signalling pathway is a crucial feature in glioblastoma, playing a pivotal role in the progression of the disease 53 .…”

Section: Discussionmentioning

confidence: 99%

“… 49 , 50 In glioblastoma, high CD99 expression has been found to promote tumour cell migration, invasion and the formation of an immune‐suppressive microenvironment. 51 , 52 Overactive activation of the EGF signalling pathway is a crucial feature in glioblastoma, playing a pivotal role in the progression of the disease. 53 Neoangiogenesis is a significant feature of tumours, and the excessive activation of the VEGF signalling pathway plays a crucial role in this process.…”

Section: Discussionmentioning

confidence: 99%

Multi‐omics analysis reveals the association between specific solute carrier proteins gene expression patterns and the immune suppressive microenvironment in glioma

Wu,

Jiang,

Zhu

et al. 2024

J Cellular Molecular Medi

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Glioma is the most prevalent malignant brain tumour. Currently, reshaping its tumour microenvironment has emerged as an appealing strategy to enhance therapeutic efficacy. As the largest group of transmembrane transport proteins, solute carrier proteins (SLCs) are responsible for the transmembrane transport of various metabolites and ions. They play a crucial role in regulating the metabolism and functions of malignant cells and immune cells within the tumour microenvironment, making them a promising target in cancer therapy. Through multidimensional data analysis and experimental validation, we investigated the genetic landscape of SLCs in glioma. We established a classification system comprising 7‐SLCs to predict the prognosis of glioma patients and their potential responses to immunotherapy and chemotherapy. Our findings unveiled specific SLC expression patterns and their correlation with the immune‐suppressive microenvironment and metabolic status. The 7‐SLC classification system was validated in distinguishing subgroups within the microenvironment, specifically identifying subsets involving malignant cells and tumour‐associated macrophages. Furthermore, the orphan protein SLC43A3, a core member of the 7‐SLC classification system, was identified as a key facilitator of tumour cell proliferation and migration, suggesting its potential as a novel target for cancer therapy.

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“…Although the exact mechanism of this upregulation of CD99 in the DMG after radiation therapy is unknown and beyond the scope of this study, the consequences of elevated CD99 expression have been shown to induce adaptability in adult glioblastoma (GBM) tumors. This adaptability is implicated in tumor recurrence and therapy resistance in these tumors (57). Our study, in conjunction with other studies, indicates that CD99 plays a crucial role in safeguarding tumor cells from radiation-induced harm.…”

Section: Discussionmentioning

confidence: 99%

“…While CD99 is implicated in other cancer types and the use of monoclonal antibody targeting CD99 has demonstrated anti-tumor efficacy in vitro and in vivo models of Ewing sarcoma, GBM, and AML, these findings, to our knowledge, have not yet resulted in clinical trials (32,(58)(59)(60). However, outcomes from previous studies investigating the oncogenic role of CD99 across diverse tumor models collectively indicate the potential clinical utility of the therapeutic antibody 10D1 in treating conditions beyond DMGs.…”

Section: Cd99 Is Expressed In a Variety Of Normal And Tumor Cells Inc...mentioning

confidence: 98%

Targeting Diffuse Midline Glioma with a novel anti-CD99 Antibody

Balakrishnan,

Madhavan,

Pierce

et al. 2024

Preprint

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Diffuse midline gliomas (DMGs) are devastating brain tumors that occur primarily in children. The salient feature of these tumors is the presence of a H3K27M mutation (K27M), associated with the worst prognosis. We identified the cell surface antigen CD99 as notably expressed in DMGs, particularly in K27M+DMGs. We found that the increased expression of CD99 in K27M+DMGs was a result of the onco-histone K27M mutation. In K27M+DMG cells, CD99 inactivation impaired tumor growth by inducing cell differentiation, indicating an oncogenic role of CD99 enabled by blocking differentiation. We then developed a novel therapeutic anti-CD99 chimeric antibody, 10D1, with a membrane-proximal binding epitope, and evaluated its antitumor efficacy in preclinical models of K27M+DMG. 10D1 suppressed DMG growth in vitro and in vivo by inducing apoptosis. When combined with radiation treatment, 10D1 exhibited improved antitumor efficiency and xenograft survival, providing a strong justification for its clinical development as a therapy for DMGs.

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Overexpression of CD99 is associated with tumor adaptiveness and indicates the tumor recurrence and therapeutic responses in gliomas

Cited by 6 publications

References 57 publications

Single-cell analysis reveals diversity of tumor-associated macrophages and their interactions with T lymphocytes in glioblastoma

Single-cell analysis reveals diversity of tumor-associated macrophages and their interactions with T lymphocytes in glioblastoma

Multi‐omics analysis reveals the association between specific solute carrier proteins gene expression patterns and the immune suppressive microenvironment in glioma

Targeting Diffuse Midline Glioma with a novel anti-CD99 Antibody

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