Research Progress About Glioma Stem Cells in the Immune Microenvironment of Glioma

Li, Xiangyu; Liu, Ming; Zhao, Jiawen; Ren, Tong; Yan, Xin; Zhang, Lijun; Wang, Xun

doi:10.3389/fphar.2021.750857

Cited by 10 publications

(8 citation statements)

References 106 publications

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“…Circulating neutrophils in the blood home to the hypoxic tumor microenvironment (TME), where they become heterogenous tumor-associated neutrophils (TANs), an essential component of immunosuppressive TME that contributes to cancer progression and therapeutic resistance 12,17 . Similar to macrophages, anti-tumor N1 and pro-tumor N2 phenotypes of TANs were found within the hypoxic TME [18][19][20][21] . Various therapeutic strategies have been developed to directly target neutrophils with a focus on neutrophil depletion or inhibition 12,22 , leading to several clinical trials (e.g., CCR5 inhibitor Maraviroc in NCT03274804).…”

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confidence: 74%

CAR-neutrophil mediated delivery of tumor-microenvironment responsive nanodrugs for glioblastoma chemo-immunotherapy

et al. 2023

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Glioblastoma (GBM) is one of the most aggressive and lethal solid tumors in human. While efficacious therapeutics, such as emerging chimeric antigen receptor (CAR)-T cells and chemotherapeutics, have been developed to treat various cancers, their effectiveness in GBM treatment has been hindered largely by the blood-brain barrier and blood-brain-tumor barriers. Human neutrophils effectively cross physiological barriers and display effector immunity against pathogens but the short lifespan and resistance to genome editing of primary neutrophils have limited their broad application in immunotherapy. Here we genetically engineer human pluripotent stem cells with CRISPR/Cas9-mediated gene knock-in to express various anti-GBM CAR constructs with T-specific CD3ζ or neutrophil-specific γ-signaling domains. CAR-neutrophils with the best anti-tumor activity are produced to specifically and noninvasively deliver and release tumor microenvironment-responsive nanodrugs to target GBM without the need to induce additional inflammation at the tumor sites. This combinatory chemo-immunotherapy exhibits superior and specific anti-GBM activities, reduces off-target drug delivery and prolongs lifespan in female tumor-bearing mice. Together, this biomimetic CAR-neutrophil drug delivery system is a safe, potent and versatile platform for treating GBM and possibly other devastating diseases.

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confidence: 74%

CAR-neutrophil mediated delivery of tumor-microenvironment responsive nanodrugs for glioblastoma chemo-immunotherapy

et al. 2023

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“…Through geospatial analyses of human GBM tumors, MDSCs were found in close proximity to CD133 + and SOX2 + GSCs; these GSCs were found to secrete the cytokine macrophage migration inhibitory factor (MIF) to recruit MDSCs ( 218 ), as well as chemokine secretion of CCL2 and CCL5 ( 15 ). Gliomas also overexpress chemokine ligands 1 and 2 (CXCL1 and CXCL2, respectively), promoting the recruitment of MDSCs from the bone marrow towards the tumor ( 227 ). A study of breast cancer found that secretion of interleukin-6 (IL-6) by tumor cells can recruit and induce an immunosuppressive phenotype in MDSCs ( 131 ).…”

Section: Gsc-immune Cell Interactions In the Tmementioning

confidence: 99%

Heterogeneity of glioblastoma stem cells in the context of the immune microenvironment and geospatial organization

et al. 2022

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Glioblastoma (GBM) is an extremely aggressive and incurable primary brain tumor with a 10-year survival of just 0.71%. Cancer stem cells (CSCs) are thought to seed GBM’s inevitable recurrence by evading standard of care treatment, which combines surgical resection, radiotherapy, and chemotherapy, contributing to this grim prognosis. Effective targeting of CSCs could result in insights into GBM treatment resistance and development of novel treatment paradigms. There is a major ongoing effort to characterize CSCs, understand their interactions with the tumor microenvironment, and identify ways to eliminate them. This review discusses the diversity of CSC lineages present in GBM and how this glioma stem cell (GSC) mosaicism drives global intratumoral heterogeneity constituted by complex and spatially distinct local microenvironments. We review how a tumor’s diverse CSC populations orchestrate and interact with the environment, especially the immune landscape. We also discuss how to map this intricate GBM ecosystem through the lens of metabolism and immunology to find vulnerabilities and new ways to disrupt the equilibrium of the system to achieve improved disease outcome.

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“…Adoptive cell therapy is a passive immunotherapy method in which a large number of amplified and activated immune cells after in vitro genetic engineering or screening activation are transfused back into the patient to enhance immune responses in the tumor microenvironment and directly or indirectly achieve tumor-killing effects (100). Unlike T cells and B cells, natural killer (NK) cells can express high levels of effector molecules with cytotoxicity, including perforin and granase B, making NK cells the most widely used in adoptive immunotherapy (100,101). However, the antitumor functions of NK cells in solid tumors are still unclear.…”

Section: Utmd-mediated Adoptive Cell Immunotherapymentioning

confidence: 99%

Ultrasound-Targeted Microbubble Destruction: Modulation in the Tumor Microenvironment and Application in Tumor Immunotherapy

et al. 2022

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Tumor immunotherapy has shown strong therapeutic potential for stimulating or reconstructing the immune system to control and kill tumor cells. It is a promising and effective anti-cancer treatment besides surgery, radiotherapy and chemotherapy. Presently, some immunotherapy methods have been approved for clinical application, and numerous others have demonstrated promising in vitro results and have entered clinical trial stages. Although immunotherapy has exhibited encouraging results in various cancer types, however, a large proportion of patients are limited from these benefits due to specific characteristics of the tumor microenvironment such as hypoxia, tumor vascular malformation and immune escape, and current limitations of immunotherapy such as off-target toxicity, insufficient drug penetration and accumulation and immune cell dysfunction. Ultrasound-target microbubble destruction (UTMD) treatment can help reduce immunotherapy-related adverse events. Using the ultrasonic cavitation effect of microstreaming, microjets and free radicals, UTMD can cause a series of changes in vascular endothelial cells, such as enhancing endothelial cells’ permeability, increasing intracellular calcium levels, regulating gene expression, and stimulating nitric oxide synthase activities. These effects have been shown to promote drug penetration, enhance blood perfusion, increase drug delivery and induce tumor cell death. UTMD, in combination with immunotherapy, has been used to treat melanoma, non-small cell lung cancer, bladder cancer, and ovarian cancer. In this review, we summarized the effects of UTMD on tumor angiogenesis and immune microenvironment, and discussed the application and progress of UTMD in tumor immunotherapy.

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Research Progress About Glioma Stem Cells in the Immune Microenvironment of Glioma

Cited by 10 publications

References 106 publications

CAR-neutrophil mediated delivery of tumor-microenvironment responsive nanodrugs for glioblastoma chemo-immunotherapy

CAR-neutrophil mediated delivery of tumor-microenvironment responsive nanodrugs for glioblastoma chemo-immunotherapy

Heterogeneity of glioblastoma stem cells in the context of the immune microenvironment and geospatial organization

Ultrasound-Targeted Microbubble Destruction: Modulation in the Tumor Microenvironment and Application in Tumor Immunotherapy

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