Role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape

Molecular Cancer, Journal Year: 2019, Volume and Issue: 18(1)

Published: Jan. 15, 2019

Tumor immune escape is an important strategy of tumor survival. There are many mechanisms escape, including immunosuppression, which has become a research hotspot in recent years. The programmed death ligand-1/programmed death-1 (PD-L1/PD-1) signaling pathway component can inhibit the activation T lymphocytes and enhance tolerance cells, thereby achieving escape. Therefore, targeting PD-L1/PD-1 attractive for cancer treatment; however, therapeutic effectiveness remains poor. This situation requires gaining deeper understanding complex varied molecular factors driving expression pathway. In this review, we summarize regulation microenvironment their roles mediating Overall, evidence accumulated to date suggests that induction PD-L1 by inflammatory may be one most affecting efficiency blocking.

Language: Английский

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The MTT Assay: Utility, Limitations, Pitfalls, and Interpretation in Bulk and Single-Cell Analysis

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(23), P. 12827 - 12827

Published: Nov. 26, 2021

The MTT assay for cellular metabolic activity is almost ubiquitous to studies of cell toxicity; however, it commonly applied and interpreted erroneously. We investigated the applicability limitations in representing treatment toxicity, viability, activity. evaluated effect potential confounding variables on measurements a prostate cancer line (PC-3) including seeding number, concentration, incubation time, serum starvation, culture media composition, released intracellular contents (cell lysate secretome), extrusion formazan extracellular space. also assessed polyethylene glycol (PEG)-coated gold nanoparticles (Au-NPs) as tested PC-3 cells measurements. additionally microscopic image cytometry tool measuring reduction at single-cell level. Our findings show that are result complicated process dependant many above-mentioned factors, therefore, optimization rational interpretation data necessary prevent misleading conclusions such and/or metabolism. conclude, with recommendations how apply perspective where utility powerful tool, but likewise has limitations.

Language: Английский

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Neoantigen vaccine: an emerging tumor immunotherapy

Molecular Cancer, Journal Year: 2019, Volume and Issue: 18(1)

Published: Aug. 23, 2019

Genetic instability of tumor cells often leads to the occurrence a large number mutations, and expression non-synonymous mutations can produce tumor-specific antigens called neoantigens. Neoantigens are highly immunogenic as they not expressed in normal tissues. They activate CD4+ CD8+ T generate immune response have potential become new targets immunotherapy. The development bioinformatics technology has accelerated identification combination different algorithms identify predict affinity neoantigens major histocompatibility complexes (MHCs) or immunogenicity is mainly based on whole-exome sequencing technology. Tumor vaccines targeting include nucleic acid, dendritic cell (DC)-based, cell, synthetic long peptide (SLP) vaccines. with checkpoint inhibition therapy radiotherapy chemotherapy might achieve better therapeutic effects. Currently, several clinical trials demonstrated safety efficacy these Further technologies algorithms, well an improvement our understanding mechanisms underlying development, will expand application neoantigen future.

Language: Английский

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Radiotheranostics in oncology: current challenges and emerging opportunities

Nature Reviews Clinical Oncology, Journal Year: 2022, Volume and Issue: 19(8), P. 534 - 550

Published: June 20, 2022

Language: Английский

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Natural killer group 2D receptor and its ligands in cancer immune escape

Molecular Cancer, Journal Year: 2019, Volume and Issue: 18(1)

Published: Feb. 27, 2019

The immune system plays important roles in tumor development. According to the immune-editing theory, escape is key survival, and exploring mechanisms of can provide a new basis for treatment tumors. In this review, we describe natural killer group 2D (NKG2D) receptor NKG2D ligand (NKG2DL) responses. Natural (NK) cells are cytotoxic system, activated on NK cell surface bind NKG2DL expressed cells, enabling activate kill cells. However, tumors clearance mediated by receptor/NKG2DL through various mechanisms. expression be regulated molecules, hypoxia microenvironment. Tumor regulate at level transcription, translation, post-translation thereby recognition particular, viruses hormones have special affect NKG2DL. Therefore, NKG2D\NKG2DL may applications as targets more effective antitumor therapy.

Language: Английский

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Dichloroacetate (DCA) and Cancer: An Overview towards Clinical Applications

Oxidative Medicine and Cellular Longevity, Journal Year: 2019, Volume and Issue: 2019, P. 1 - 14

Published: Nov. 14, 2019

An extensive body of literature describes anticancer property dichloroacetate (DCA), but its effective clinical administration in cancer therapy is still limited to trials. The occurrence side effects such as neurotoxicity well the suspicion DCA carcinogenicity restricts use DCA. However, last years, number reports supporting employment against increased also because great interest targeting metabolism tumour cells. Dissecting mechanism action helped understand bases selective efficacy A successful coadministration with conventional chemotherapy, radiotherapy, other drugs, or natural compounds has been tested several models. New drug delivery systems and multiaction containing drugs seem ameliorate bioavailability appear more efficient thanks a synergistic multiple agents. spread efficiency prompted additional studies that let find potential molecular targets Interestingly, could significantly affect stem cell fraction contribute eradication. Collectively, these findings provide strong rationale towards novel translational therapy.

Language: Английский

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Communication between mitochondria and other organelles: a brand-new perspective on mitochondria in cancer

Cell & Bioscience, Journal Year: 2019, Volume and Issue: 9(1)

Published: March 19, 2019

Mitochondria are energy factories of cells and important pivots for intracellular interactions with other organelles. They interact the endoplasmic reticulum, peroxisomes, nucleus through signal transduction, vesicle transport, membrane contact sites to regulate metabolism, biosynthesis, immune response, cell turnover. However, when communication between organelles fails mitochondria dysfunctional, it may induce tumorigenesis. In this review, we elaborate on how nuclei, as well relation organelle tumor development .

Language: Английский

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Application of atomic force microscopy in cancer research

Journal of Nanobiotechnology, Journal Year: 2018, Volume and Issue: 16(1)

Published: Dec. 1, 2018

Atomic force microscopy (AFM) allows for nanometer-scale investigation of cells and molecules. Recent advances have enabled its application in cancer research diagnosis. The physicochemical properties live undergo changes when their physiological conditions are altered. These can therefore reflect complex processes occurring cells. When the process carcinogenesis stimulated by external stimuli, morphology, elasticity, adhesion may change. AFM perform surface imaging ultrastructural observation with atomic resolution under near-physiological conditions, collecting spectroscopy information which study mechanical For this reason, has potential to be used as a tool high into ultrastructure tumor This review describes working principle, mode, technical points microscopy, reviews applications prospects research.

Language: Английский

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Interfering with Tumor Hypoxia for Radiotherapy Optimization

Journal of Experimental & Clinical Cancer Research, Journal Year: 2021, Volume and Issue: 40(1)

Published: June 21, 2021

Hypoxia in solid tumors is an important predictor of treatment resistance and poor clinical outcome. The significance hypoxia the development to radiotherapy has been recognized for decades search hypoxia-targeting, radiosensitizing agents continues. This review summarizes main hypoxia-related processes relevant on subcellular, cellular tissue level discusses radiation oncology, especially with regard current shift towards hypofractionated regimens. Furthermore, we discuss strategies interfere optimization, highlight novel insights into molecular pathways involved that might be utilized increase efficacy radiotherapy.

Language: Английский

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Regulatory pathways and drugs associated with ferroptosis in tumors

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(6)

Published: June 10, 2022

Abstract Ferroptosis is a type of cell death that depends on iron and reactive oxygen species (ROS). The accumulation lipid peroxidation primarily initiates oxidative membrane damage during ferroptosis. core molecular mechanism ferroptosis includes the regulation oxidation balance between antioxidant defense. Tumor cells usually contain large amount H 2 O , ferrous/iron ions will react with excessive in to produce hydroxyl radicals induce tumor cells. Here, we reviewed latest studies introduced tumor-related signaling pathways We paid particular attention role noncoding RNA, nanomaterials, drugs, targeted treatment using drugs for mediating process Finally, discussed currently unresolved problems future research directions prospects this emerging field. Therefore, have attempted provide reference further understanding pathogenesis proposed new targets cancer treatment.

Language: Английский

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