Role of tumor microenvironment in the regulation of PD‐L1: A novel role in resistance to cancer immunotherapy

Khandani, Nirvana Kalantari; Ghahremanloo, Atefeh; Hashemy, Seyed Isaac

doi:10.1002/jcp.29671

Cited by 24 publications

(14 citation statements)

References 174 publications

(164 reference statements)

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“…Tumor cells bind to PD-1 on tumor-infiltrating lymphocytes via PD-L1. This interaction induces lymphocyte apoptosis, allowing tumor cells to resist destruction and achieve immune escape [ 70 , 71 ]. The PD-L1/PD-1 signaling axis mediates immune escape in the tumor microenvironment [ 68 ]; PD-L1 is selectively expressed on the surface of cancer cells, and its binding to PD-1 on the surface of activated T cells results in negative regulatory signal transmission, which decreases immune activity [ 72 , 73 ].…”

Section: Tumor Immune Escapementioning

confidence: 99%

Hypoxia-inducible factors: master regulators of hypoxic tumor immune escape

et al. 2022

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Hypoxia, a common feature of the tumor microenvironment in various types of cancers, weakens cytotoxic T cell function and causes recruitment of regulatory T cells, thereby reducing tumoral immunogenicity. Studies have demonstrated that hypoxia and hypoxia-inducible factors (HIFs) 1 and 2 alpha (HIF1A and HIF2A) are involved in tumor immune escape. Under hypoxia, activation of HIF1A induces a series of signaling events, including through programmed death receptor-1/programmed death ligand-1. Moreover, hypoxia triggers shedding of complex class I chain-associated molecules through nitric oxide signaling impairment to disrupt immune surveillance by natural killer cells. The HIF-1-galactose-3-O-sulfotransferase 1-sulfatide axis enhances tumor immune escape via increased tumor cell-platelet binding. HIF2A upregulates stem cell factor expression to recruit tumor-infiltrating mast cells and increase levels of cytokines interleukin-10 and transforming growth factor-β, resulting in an immunosuppressive tumor microenvironment. Additionally, HIF1A upregulates expression of tumor-associated long noncoding RNAs and suppresses immune cell function, enabling tumor immune escape. Overall, elucidating the underlying mechanisms by which HIFs promote evasion of tumor immune surveillance will allow for targeting HIF in tumor treatment. This review discusses the current knowledge of how hypoxia and HIFs facilitate tumor immune escape, with evidence to date implicating HIF1A as a molecular target in such immune escape. This review provides further insight into the mechanism of tumor immune escape, and strategies for tumor immunotherapy are suggested.

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Section: Tumor Immune Escapementioning

confidence: 99%

Hypoxia-inducible factors: master regulators of hypoxic tumor immune escape

et al. 2022

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“…The immunosuppressive TME is known to help the cancer cells evade the immune system (126). For example, apoptotic tumor cells are rarely recognized as antigens, and TME has the ability to upregulate the expression of regulatory T (Treg) cells or myeloidderived suppressor cells and downregulate that of the cytotoxic T cells (127).…”

Section: Use Of Exosome In Combination With Cancer Immunotherapymentioning

confidence: 99%

Exosomes as Smart Nanoplatforms for Diagnosis and Therapy of Cancer

et al. 2021

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Exosomes are composed of a lipid bilayer membrane, containing proteins, nucleic acids, DNA, RNA, etc., derived from donor cells. They have a size range of approximately 30-150 nm. The intrinsic characteristics of exosomes, including efficient cellular uptake, low immunogenicity, low toxicity, intrinsic ability to traverse biological barriers, and inherent targeting ability, facilitate their application to the drug delivery system. Here, we review the generation, uptake, separation, and purification methods of exosomes, focusing on their application as carriers in tumor diagnosis and treatment, especially in brain tumors, as well as the patent applications of exosomes in recent years.

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“…Microvesicles originate directly from the budding of plasma cellular membranes and range in size from 200 to 1000 nm. The smallest EVs derived from endosomes with 30–150 nm diameter are called exosomes, in which different microenvironmental conditions can affect different amounts of exosome production and also various components at the cargo level. , Extensive studies have reported the critical role of exosomes in immune regulation, differentiation, apoptosis, angiogenesis through passing immunomodulatory cytokines, and noncoding RNAs (ncRNAs) like miRNAs between immune cells and other cell populations. − Notably, several ncRNAs can be transferred by exosomes including microRNA (miRNAs), long noncoding RNA (lncRNAs), and circular RNA (circRNAs), which are the most attractive because of their role in intercellular communication …”

Section: Introductionmentioning

confidence: 99%

Exosomes as Neurological Nanosized Machines

et al. 2022

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In the past few decades, nanomedicine research has advanced dramatically. In spite of this, traditional nanomedicine faces major obstacles, such as blood–brain barriers, low concentrations at target sites, and rapid removal from the body. Exosomes as natural extracellular vesicles contain special bioactive molecules for cell-to-cell communications and nervous tissue function, which could overcome the challenges of nanoparticles. Most recently, microRNAs, long noncoding RNA, and circulating RNA of exosomes have been appealing because of their critical effect on the molecular pathway of target cells. In this review, we have summarized the important role of exosomes of noncoding RNAs in the occurrence of brain diseases.

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Role of tumor microenvironment in the regulation of PD‐L1: A novel role in resistance to cancer immunotherapy

Cited by 24 publications

References 174 publications

Hypoxia-inducible factors: master regulators of hypoxic tumor immune escape

Hypoxia-inducible factors: master regulators of hypoxic tumor immune escape

Exosomes as Smart Nanoplatforms for Diagnosis and Therapy of Cancer

Exosomes as Neurological Nanosized Machines

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