Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Oct. 7, 2021

Abstract Myeloid-derived suppressor cells (MDSCs) are a heterogenic population of immature myeloid with immunosuppressive effects, which undergo massive expansion during tumor progression. These not only support immune escape directly but also promote invasion via various non-immunological activities. Besides, this group proved to impair the efficiency current antitumor strategies such as chemotherapy, radiotherapy, and immunotherapy. Therefore, MDSCs considered potential therapeutic targets for cancer therapy. Treatment targeting have shown promising outcomes in both preclinical studies clinical trials when administrated alone, or combination other anticancer therapies. In review, we shed new light on recent advances biological characteristics functions MDSCs. We hope propose an overview MDSCs-targeting therapies so provide ideas treatment.

Language: Английский

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Metabolic communication in the tumour–immune microenvironment

Nature Cell Biology, Journal Year: 2022, Volume and Issue: 24(11), P. 1574 - 1583

Published: Oct. 13, 2022

Language: Английский

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Indoleamine 2,3‐dioxygenase 1 (IDO1): an up‐to‐date overview of an eclectic immunoregulatory enzyme

FEBS Journal, Journal Year: 2021, Volume and Issue: 289(20), P. 6099 - 6118

Published: June 19, 2021

Indoleamine 2,3‐dioxygenase 1 (IDO1) catalyzes the initial rate‐limiting step in degradation of essential amino acid tryptophan along kynurenine pathway. When discovered more than 50 years ago, IDO1 was thought to be an effector molecule capable mediating a survival strategy based on deprivation bacteria and tumor cells tryptophan. Since 1998, when catabolism crucially involved maintenance maternal T‐cell tolerance, has become focus several laboratories around world. Indeed, is now considered as authentic immune regulator not only pregnancy, but also autoimmune diseases, chronic inflammation, immunity. However, last years, bulk new information—including structural, biological, functional evidence—on come light. For instance, we know that peculiar conformational plasticity and, addition complex highly regulated catalytic activity, performing nonenzymic function reprograms expression profile toward immunoregulatory phenotype. With this state‐of‐the‐art review, aimed at gathering most recent information obtained for eclectic protein well highlighting major unresolved questions.

Language: Английский

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Reshaping the systemic tumor immune environment (STIE) and tumor immune microenvironment (TIME) to enhance immunotherapy efficacy in solid tumors

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: July 7, 2022

The development of combination immunotherapy based on the mediation regulatory mechanisms tumor immune microenvironment (TIME) is promising. However, a deep understanding immunology must involve systemic environment (STIE) which was merely illustrated previously. Here, we aim to review recent advances in single-cell transcriptomics and spatial for studies STIE, TIME, their interactions, may reveal heterogeneity responses as well dynamic changes essential treatment effect. We evidence from preclinical clinical related significance overall survival, through different immunomodulatory pathways, such metabolic neuro-immunological pathways. also evaluate interactions after local radiotherapy or combined immunotherapy. focus our lung cancer, hepatocellular carcinoma, nasopharyngeal aiming reshape STIE TIME enhance efficacy.

Language: Английский

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Aptamer-conjugated nano-liposome for immunogenic chemotherapy with reversal of immunosuppression

Journal of Controlled Release, Journal Year: 2022, Volume and Issue: 348, P. 893 - 910

Published: June 29, 2022

Language: Английский

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Kynurenine importation by SLC7A11 propagates anti-ferroptotic signaling

Molecular Cell, Journal Year: 2022, Volume and Issue: 82(5), P. 920 - 932.e7

Published: March 1, 2022

Language: Английский

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Exploiting innate immunity for cancer immunotherapy

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Nov. 27, 2023

Abstract Immunotherapies have revolutionized the treatment paradigms of various types cancers. However, most these immunomodulatory strategies focus on harnessing adaptive immunity, mainly by inhibiting immunosuppressive signaling with immune checkpoint blockade, or enhancing immunostimulatory bispecific T cell engager and chimeric antigen receptor (CAR)-T cell. Although agents already achieved great success, only a tiny percentage patients could benefit from immunotherapies. Actually, immunotherapy efficacy is determined multiple components in tumor microenvironment beyond immunity. Cells innate arm system, such as macrophages, dendritic cells, myeloid-derived suppressor neutrophils, natural killer unconventional also participate cancer evasion surveillance. Considering that cornerstone antitumor response, utilizing immunity provides potential therapeutic options for control. Up to now, exploiting agonists stimulator interferon genes, CAR-macrophage -natural therapies, metabolic regulators, novel exhibited potent activities preclinical clinical studies. Here, we summarize latest insights into roles cells discuss advances arm-targeted strategies.

Language: Английский

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Beyond CTLA-4 and PD-1 Inhibition: Novel Immune Checkpoint Molecules for Melanoma Treatment

Cancers, Journal Year: 2023, Volume and Issue: 15(10), P. 2718 - 2718

Published: May 11, 2023

More than ten years after the approval of ipilimumab, immune checkpoint inhibitors (ICIs) against PD-1 and CTLA-4 have been established as most effective treatment for locally advanced or metastatic melanoma, achieving durable responses either monotherapies in combinatorial regimens. However, a considerable proportion patients do not respond experience early relapse, due to multiple parameters that contribute melanoma resistance. The expression other checkpoints beyond molecules remains major mechanism evasion. recent anti-LAG-3 ICI, relatlimab, combination with nivolumab disease, has capitalized on extensive research field highlighted potential further improvement prognosis by synergistically blocking additional targets new ICI-doublets, antibody-drug conjugates, novel modalities. Herein, we provide comprehensive overview presently published molecules, including LAG-3, TIGIT, TIM-3, VISTA, IDO1/IDO2/TDO, CD27/CD70, CD39/73, HVEM/BTLA/CD160 B7-H3. Beginning from their immunomodulatory properties co-inhibitory co-stimulatory receptors, present all therapeutic modalities targeting these tested preclinical clinical settings. Better understanding checkpoint-mediated crosstalk between effector cells is essential generating more strategies augmented response.

Language: Английский

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Involvement of tumor immune microenvironment metabolic reprogramming in colorectal cancer progression, immune escape, and response to immunotherapy

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: July 25, 2024

Metabolic reprogramming is a k`ey hallmark of tumors, developed in response to hypoxia and nutrient deficiency during tumor progression. In both cancer immune cells, there metabolic shift from oxidative phosphorylation (OXPHOS) aerobic glycolysis, also known as the Warburg effect, which then leads lactate acidification, increased lipid synthesis, glutaminolysis. This facilitates evasion and, within microenvironment (TME), cells collaborate create suppressive (TIME). The growing interest TME, particularly its significance colorectal (CRC)-one most prevalent cancers-has prompted us explore this topic. CRC exhibits abnormal glutaminolysis, synthesis. Acidosis hampers activity anti-tumor inhibits phagocytosis tumor-associated macrophages (TAMs), while promotes development regulatory T (Tregs) M2-like macrophages. activation G-protein coupled receptor 81 (GPR81) signaling overexpression programmed death-ligand 1 (PD-L1) reduces antigen presentation capability dendritic cells. Moreover, genetic epigenetic cell phenotype, along with microbiota, significantly influence reprogramming. Activating RAS mutations epidermal growth factor (EGFR) occur approximately 50% 80% patients, respectively, stimulating glycolysis increasing levels hypoxia-inducible alpha (HIF-1α) MYC proteins. Certain bacteria produce short-chain fatty acids (SCFAs), activate CD8+ genes involved processing presentation, other mechanisms support pro-tumor activities. use checkpoint inhibitors (ICIs) selected patients has shown promise, combination these drugs that inhibit currently being intensively researched enhance efficacy immunotherapy.

Language: Английский

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Placenta: an old organ with new functions

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: April 19, 2024

The transition from oviparity to viviparity and the establishment of feto-maternal communications introduced placenta as major anatomical site provide nutrients, gases, hormones developing fetus. has endocrine functions, orchestrates maternal adaptations pregnancy at different periods pregnancy, acts a selective barrier minimize exposure fetus xenobiotics, pathogens, parasites. Despite fact that this ancient organ is central for normal in eutherians, remains one least studied organs. first step embryo implantation, finely regulated by trophoectoderm, precursor all trophoblast cells. There bidirectional communication between endometrium leading decidualization, critical maintenance pregnancy. are three-direction interactions placenta, immune cells, adaptation endometrial system allogeneic While 65% systemically expressed human proteins have been found tissues, it expresses numerous placenta-specific proteins, whose expression dramatically changed gestational diseases could serve biomarkers early detection diseases. Surprisingly, placentation carcinogenesis exhibit shared features metabolism cell behavior, molecular signatures, signaling pathways, tissue microenvironment, which proposes concept "cancer ectopic trophoblastic cells". By extensive researches novel field, handful cancer discovered. This review paper, inspired part our experiences during past couple years, highlights new aspects placental functions with emphasis on its immunomodulatory role successful potential link carcinogenesis.

Language: Английский

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