Tumor microenvironment: barrier or opportunity towards effective cancer therapy

Journal of Biomedical Science, Journal Year: 2022, Volume and Issue: 29(1)

Published: Oct. 17, 2022

Abstract Tumor microenvironment (TME) is a specialized ecosystem of host components, designed by tumor cells for successful development and metastasis tumor. With the advent 3D culture advanced bioinformatic methodologies, it now possible to study TME’s individual components their interplay at higher resolution. Deeper understanding immune cell’s diversity, stromal constituents, repertoire profiling, neoantigen prediction TMEs has provided opportunity explore spatial temporal regulation therapeutic interventions. The variation TME composition among patients plays an important role in determining responders non-responders towards cancer immunotherapy. Therefore, there could be possibility reprogramming overcome widely prevailing issue immunotherapeutic resistance. focus present review understand complexity comprehending future perspective its as potential targets. later part describes sophisticated models emerging valuable means extensive account tools profile predict neoantigens. Overall, this provides comprehensive current knowledge available target TME.

Language: Английский

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RNA modifications: importance in immune cell biology and related diseases

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Sept. 22, 2022

RNA modifications have become hot topics recently. By influencing processes, including generation, transportation, function, and metabolization, they act as critical regulators of cell biology. The immune abnormality in human diseases is also a research focus progressing rapidly these years. Studies demonstrated that participate the multiple biological processes cells, development, differentiation, activation, migration, polarization, thereby modulating responses are involved some related diseases. In this review, we present existing knowledge functions underlying mechanisms modifications, N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), N4-acetylcytosine (ac4C), pseudouridine (Ψ), uridylation, adenosine-to-inosine (A-to-I) editing, summarize their roles Via regulating can pathogenesis diseases, such cancers, infection, inflammatory autoimmune We further highlight challenges future directions based on knowledge. All all, review will provide helpful well novel ideas for researchers area.

Language: Английский

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Lupeol and its derivatives as anticancer and anti-inflammatory agents: Molecular mechanisms and therapeutic efficacy

Pharmacological Research, Journal Year: 2020, Volume and Issue: 164, P. 105373 - 105373

Published: Dec. 11, 2020

Language: Английский

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Epigenetic regulation in the tumor microenvironment: molecular mechanisms and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 22, 2023

Abstract Over decades, researchers have focused on the epigenetic control of DNA-templated processes. Histone modification, DNA methylation, chromatin remodeling, RNA and noncoding RNAs modulate many biological processes that are crucial to development cancers. Dysregulation epigenome drives aberrant transcriptional programs. A growing body evidence suggests mechanisms modification dysregulated in human cancers might be excellent targets for tumor treatment. Epigenetics has also been shown influence immunogenicity immune cells involved antitumor responses. Thus, application therapy cancer immunotherapy their combinations may important implications Here, we present an up-to-date thorough description how modifications cell responses microenvironment (TME) epigenetics internally modify TME. Additionally, highlight therapeutic potential targeting regulators immunotherapy. Harnessing complex interplay between immunology develop therapeutics combine thereof is challenging but could yield significant benefits. The purpose this review assist understanding impact TME, so better immunotherapies can developed.

Language: Английский

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The RNA m6A reader YTHDF2 controls NK cell antitumor and antiviral immunity

The Journal of Experimental Medicine, Journal Year: 2021, Volume and Issue: 218(8)

Published: June 23, 2021

N 6-methyladenosine (m6A) is the most prevalent posttranscriptional modification on RNA. NK cells are predominant innate lymphoid that mediate antiviral and antitumor immunity. However, whether how m6A modifications affect cell immunity remain unknown. Here, we discover YTHDF2, a well-known reader, upregulated in upon activation by cytokines, tumors, cytomegalovirus infection. Ythdf2 deficiency impairs activity vivo. YTHDF2 maintains homeostasis terminal maturation, correlating with modulating trafficking regulating Eomes, respectively. promotes effector function required for IL-15-mediated survival proliferation forming STAT5-YTHDF2 positive feedback loop. Transcriptome-wide screening identifies Tardbp to be involved or as YTHDF2-binding target cells. Collectively, elucidate biological roles of highlight new direction harness

Language: Английский

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Current Perspectives on “Off-The-Shelf” Allogeneic NK and CAR-NK Cell Therapies

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Dec. 1, 2021

Natural killer cells (NK cells) are the first line of innate immune defense system, primarily located in peripheral circulation and lymphoid tissues. They kill virally infected malignant through a balancing play inhibitory stimulatory receptors. In pre-clinical investigational studies, NK show promising anti-tumor effects used adoptive transfer activated expanded cells, ex-vivo . express co-stimulatory molecules that attractive targets for immunotherapy cancers. Recent clinical trials investigating use CAR-NK different cancers to determine efficiency. Herein, we review cell therapy approaches preparation from tissue sources, ways expansion “off-the-shelf” allogeneic cell-doses therapies, how vector delivery systems engineer with CARs) cancer immunotherapy.

Language: Английский

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Cell Membrane-Coated Mimics: A Methodological Approach for Fabrication, Characterization for Therapeutic Applications, and Challenges for Clinical Translation

ACS Nano, Journal Year: 2021, Volume and Issue: 15(11), P. 17080 - 17123

Published: Oct. 26, 2021

Cell membrane-coated (CMC) mimics are micro/nanosystems that combine an isolated cell membrane and a template of choice to mimic the functions cell. The design exploits its physicochemical biological properties for therapeutic applications. demonstrate excellent compatibility, enhanced biointerfacing capabilities, physical, chemical, tunability, ability retain cellular properties, immune escape, prolonged circulation time, protect encapsulated drug from degradation active targeting. These ease adapting them personalized clinical medicine have generated significant research interest over past decade. This review presents detailed overview recent advances in development mimics. primary focus is collate discuss components, fabrication methodologies, significance physiochemical characterization techniques validating CMC mimic. We present critical analysis two main components mimics: mapped their use scenarios. In addition, we emphasized on challenges associated with translation. Overall, this up date toolbox researchers can benefit while designing characterizing

Language: Английский

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Natural killer cells: a promising immunotherapy for cancer

Journal of Translational Medicine, Journal Year: 2022, Volume and Issue: 20(1)

Published: May 23, 2022

Abstract As a promising alternative platform for cellular immunotherapy, natural killer cells (NK) have recently gained attention as an important type of innate immune regulatory cell. NK can rapidly kill multiple adjacent cancer through non-MHC-restrictive effects. Although tumors may develop resistance mechanisms to endogenous cell attack, in vitro activation, expansion, and genetic modification greatly enhance their anti-tumor activity give them the ability overcome drug resistance. Some these approaches been translated into clinical applications, trials infusion patients with hematological malignancies solid thus far yielded many encouraging results. CAR-T exhibited great success treating malignancies, but drawbacks include high manufacturing costs potentially fatal toxicity, such cytokine release syndrome. To issues, CAR-NK were generated engineering demonstrated significant responses lower adverse effects compared therapy. In this review, we summarize recent advances focusing on biology function, types therapy, future perspectives

Language: Английский

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Effects of Glucose Metabolism, Lipid Metabolism, and Glutamine Metabolism on Tumor Microenvironment and Clinical Implications

Biomolecules, Journal Year: 2022, Volume and Issue: 12(4), P. 580 - 580

Published: April 14, 2022

In recent years, an increasingly more in depth understanding of tumor metabolism tumorigenesis, growth, metastasis, and prognosis has been achieved. The broad heterogeneity tissue is the critical factor affecting outcome treatment. Metabolic not only found cells but also their surrounding immune stromal cells; for example, many suppressor cells, such as tumor-associated macrophages (TAMs), myeloid-derived (MDSCs), T-lymphocytes. Abnormalities often lead to short survival or resistance antitumor therapy, e.g., chemotherapy, radiotherapy, targeted immunotherapy. Using metabolic characteristics microenvironment identify treat cancer become a great research hotspot. This review systematically addresses impacts on effector represents advances effects other microenvironment. Finally, we introduce some applications features clinical oncology.

Language: Английский

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Allosteric Regulation of IGF2BP1 as a Novel Strategy for the Activation of Tumor Immune Microenvironment

ACS Central Science, Journal Year: 2022, Volume and Issue: 8(8), P. 1102 - 1115

Published: May 17, 2022

Tumor immune microenvironment (TIME) regulators are promising cancer immunotherapeutic targets. IGF2BP1, as a crucial N6-methyladenosine (m6A) reader protein, recognizes m6A target transcripts, ultimately leading to development. However, currently, the biological function of IGF2BP1 in regulating TIME is not well-understood. In this study, we report that knockdown induces cell apoptosis, thereby significantly only activating infiltration including CD4+, CD8+ T cells, CD56+ NK and F4/80+ macrophage but also decreasing PD-L1 expression hepatocellular carcinoma (HCC). Then, chemical genetics identifies small-molecule cucurbitacin B (CuB), which directly targets at unique site (Cys253) KH1-2 domains. This leads pharmacological allosteric effect block recognition mRNA such c-MYC, highly associated with apoptosis response. vivo, CuB exhibits an obvious anti-HCC through inducing subsequently recruits cells tumor well blocking expression. Collectively, may serve novel for anticancer therapeutics via mediating TIME.

Language: Английский

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