CRISPR-Cas9–Mediated TIM3 Knockout in Human Natural Killer Cells Enhances Growth Inhibitory Effects on Human Glioma Cells

Morimoto, Takayuki; Nakazawa, Tsutomu; Matsuda, Ryosuke; Nishimura, Fusanori; Nakamura, Mitsutoshi; Yamada, Shuichi; Nakagawa, Ichiro; Park, Young-Soo; Tsujimura, Takahiro; Nakase, Hiroyuki

doi:10.3390/ijms22073489

Cited by 37 publications

(35 citation statements)

References 57 publications

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“…Over the last few years, with the constant emergence of modern technologies such as CRISPR/Cas9-mediated target gene activation ( Xie et al, 2019 ; Morimoto and Nakazawa, 2021 ) and single cell RNA sequencing ( Tirosh and Suvà, 2018 ), the characterization of GBM genome, epigenome, transcriptome revealed multiple subtypes and high inter- and intra-tumor heterogeneity of GBM ( DeCordova et al, 2020 ). Glioma is a highly complex systemic disease that develops as a product of long-term Tumor/TME crosstalk between glioma cells and their local and distant microenvironments.…”

Section: Discussionmentioning

confidence: 99%

Tumor Associated Macrophages, as the Dominant Immune Cells, Are an Indispensable Target for Immunologically Cold Tumor—Glioma Therapy?

Tong

et al. 2021

Front. Cell Dev. Biol.

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Tumor microenvironment (TME) is the cornerstone of the occurrence, development, invasion and diffusion of the malignant central nerve system (CNS) tumor, glioma. As the largest number of inflammatory cells in glioma TME, tumor associated macrophages (TAMs) and their secreted factors are indispensable to the progression of glioma, which is a well-known immunologically “cold” tumor, including the growth of tumor cells, invasion, migration, angiogenesis, cancer immunosuppression and metabolism. TAMs intimately interface with the treatment failure and poor prognosis of glioma patients, and their density increases with increasing glioma grade. Recently, great progress has been made in TAM-targeting for anti-tumor therapy. According to TAMs’ function in tumorigenesis and progression, the major anti-tumor treatment strategies targeting TAMs are to hinder macrophage recruitment in TME, reduce TAMs viability or remodel TAMs phenotype from M2 to M1. Different approaches offer unique and effective anti-tumor effect by regulating the phagocytosis, polarization and pro-tumor behaviors of macrophages in the therapy of glioma. The present review summarizes the significant characteristics and related mechanisms of TAMs and addresses the related research progress on targeting TAMs in glioma.

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Section: Discussionmentioning

confidence: 99%

Tumor Associated Macrophages, as the Dominant Immune Cells, Are an Indispensable Target for Immunologically Cold Tumor—Glioma Therapy?

Tong

et al. 2021

Front. Cell Dev. Biol.

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“…Gene editing was also tested to increase CD8+ T lymphocytes’ efficiency in targeting and destroying GBM tumor cells by identifying putative membrane target proteins [ 296 ]. Recently, gene editing of natural killer (NK) lymphocytes showed promising results in enhancing cytotoxicity against glioblastoma cells [ 297 , 298 ]. Recently used and approved by FDA as a treatment for multiple refractory myeloma, gene editing of patients’ T-cells will most likely become the next gold standard of care in aggressive cancers, including GBM.…”

Section: Cell Therapy—a Novel Avenue To Pursue In Gbmmentioning

confidence: 99%

Friends with Benefits: Chemokines, Glioblastoma-Associated Microglia/Macrophages, and Tumor Microenvironment

Codrici

Popescu

Tănase

et al. 2022

IJMS

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Glioma is the most common primary intracranial tumor and has the greatest prevalence of all brain tumors. Treatment resistance and tumor recurrence in GBM are mostly explained by considerable alterations within the tumor microenvironment, as well as extraordinary cellular and molecular heterogeneity. Soluble factors, extracellular matrix components, tissue-resident cell types, resident or newly recruited immune cells together make up the GBM microenvironment. Regardless of many immune cells, a profound state of tumor immunosuppression is supported and developed, posing a considerable hurdle to cancer cells’ immune-mediated destruction. Several studies have suggested that various GBM subtypes present different modifications in their microenvironment, although the importance of the microenvironment in treatment response has yet to be determined. Understanding the microenvironment and how it changes after therapies is critical because it can influence the remaining invasive GSCs and lead to recurrence. This review article sheds light on the various components of the GBM microenvironment and their roles in tumoral development, as well as immune-related biological processes that support the interconnection/interrelationship between different cell types. Also, we summarize the current understanding of the modulation of soluble factors and highlight the dysregulated inflammatory chemokine/specific receptors cascades/networks and their significance in tumorigenesis, cancer-related inflammation, and metastasis.

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“…Other trials with the same objective are in progress (NCT0374796, NCT 03545815). In this scenario, some targets have been recently searched in NK cells, alone or in combinatorial settings (multiplex), as a proof of concept for the molecular function, methodological efficiency, and feasibility of NK immunotherapy designs, including TIGIT, CD96, DNAM-1, NKG2A, and TIM-3 [ 259 , 385 , 386 ], along with other regulators of NK cell activity [ 173 , 387 ].…”

Section: Nk-cell-based Immunotherapymentioning

confidence: 99%

The War Is on: The Immune System against Glioblastoma—How Can NK Cells Drive This Battle?

et al. 2022

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Natural killer (NK) cells are innate lymphocytes that play an important role in immunosurveillance, acting alongside other immune cells in the response against various types of malignant tumors and the prevention of metastasis. Since their discovery in the 1970s, they have been thoroughly studied for their capacity to kill neoplastic cells without the need for previous sensitization, executing rapid and robust cytotoxic activity, but also helper functions. In agreement with this, NK cells are being exploited in many ways to treat cancer. The broad arsenal of NK-based therapies includes adoptive transfer of in vitro expanded and activated cells, genetically engineered cells to contain chimeric antigen receptors (CAR-NKs), in vivo stimulation of NK cells (by cytokine therapy, checkpoint blockade therapies, etc.), and tumor-specific antibody-guided NK cells, among others. In this article, we review pivotal aspects of NK cells’ biology and their contribution to immune responses against tumors, as well as providing a wide perspective on the many antineoplastic strategies using NK cells. Finally, we also discuss those approaches that have the potential to control glioblastoma—a disease that, currently, causes inevitable death, usually in a short time after diagnosis.

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CRISPR-Cas9–Mediated TIM3 Knockout in Human Natural Killer Cells Enhances Growth Inhibitory Effects on Human Glioma Cells

Cited by 37 publications

References 57 publications

Tumor Associated Macrophages, as the Dominant Immune Cells, Are an Indispensable Target for Immunologically Cold Tumor—Glioma Therapy?

Tumor Associated Macrophages, as the Dominant Immune Cells, Are an Indispensable Target for Immunologically Cold Tumor—Glioma Therapy?

Friends with Benefits: Chemokines, Glioblastoma-Associated Microglia/Macrophages, and Tumor Microenvironment

The War Is on: The Immune System against Glioblastoma—How Can NK Cells Drive This Battle?

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