Mechanisms underlying low-clinical responses to PD-1/PD-L1 blocking antibodies in immunotherapy of cancer: a key role of exosomal PD-L1

Journal for ImmunoTherapy of Cancer, Journal Year: 2021, Volume and Issue: 9(1), P. e001698 - e001698

Published: Jan. 1, 2021

Exosomes, as the main group of extracellular vesicles, are biologically active lipid-bilayer vesicles that naturally released from different types normal or tumor cells. These play an important role in intercellular communication and influence environment immune system. Emerging evidence demonstrates cancer-derived exosomes enriched immunosuppressive proteins, such programmed death-ligand 1 (PD-L1). PD-L1 its receptor cell death protein (PD-1) key checkpoint molecules promote progression via negative regulation responses. PDL-1 is highly expressed on surface cells binds to PD-1 activated T cells, leading suppression which consequently enables cancer escape antitumor immunity. Currently, there several Food Drug Administration-approved monoclonal antibodies blocking PD-1/PD-L1 interaction, clinically used for treatment. However, despite impressive treatment outcomes, some patients show poor response blockade. Of note, tumor-derived containing can recapitulate effect cell-surface PD-L1. There reveals a significant association between levels circulating exosomal rate anti-PD-1/PD-L1 antibody therapy. The present article reviews therapeutic resistance Importantly, it suggested removal could serve adjuvant enhancing efficacy therapy with cancer.

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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Combine and conquer: manganese synergizing anti-TGF-β/PD-L1 bispecific antibody YM101 to overcome immunotherapy resistance in non-inflamed cancers

Journal of Hematology & Oncology, Journal Year: 2021, Volume and Issue: 14(1)

Published: Sept. 15, 2021

Our previous work showed that the anti-TGF-β/PD-L1 bispecific antibody YM101 effectively overcame anti-PD-L1 resistance in immune-excluded tumor models. However, immune-desert models, efficacy of was limited. Bivalent manganese (Mn

Language: Английский

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Insights from a 30-year journey: function, regulation and therapeutic modulation of PD1

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 23(10), P. 682 - 695

Published: April 25, 2023

Language: Английский

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COX 2-inhibitors; a thorough and updated survey into combinational therapies in cancers

Medical Oncology, Journal Year: 2024, Volume and Issue: 41(1)

Published: Jan. 2, 2024

Language: Английский

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The role of microRNAs in the gastric cancer tumor microenvironment

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Aug. 20, 2024

Gastric cancer (GC) is one of the deadliest malignant tumors with unknown pathogenesis. Due to its treatment resistance, high recurrence rate, and lack reliable early detection techniques, a majority patients have poor prognosis. Therefore, identifying new tumor biomarkers therapeutic targets essential. This review aims provide fresh insights into enhancing prognosis GC by summarizing processes through which microRNAs (miRNAs) regulate microenvironment (TME) highlighting their critical role in TME. A comprehensive literature was conducted focusing on interactions among cells, extracellular matrix, blood vessels, cancer-associated fibroblasts, immune cells within The noncoding RNAs, known as miRNAs, modulating TME various signaling pathways, cytokines, growth factors, exosomes specifically examined. Tumor formation, metastasis, therapy are significantly influenced miRNAs progression these multiple exosomes. Dysregulation affects cellular such cell proliferation, differentiation, angiogenesis, contributing pathogenesis GC. play crucial regulation TME, influencing patient By understanding mechanisms control potential can be identified improve

Language: Английский

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Harnessing the power of exosomes for diagnosis, prognosis, and treatment of hematological malignancies

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 7, 2025

Exosomes are small extracellular vesicles of endocytic origin released by various cell types. They consist lipid bilayers containing macromolecules such as lipids, proteins, microRNAs, growth factors, cytokines, and carbohydrates. play a critical role in the diagnosis treatment diseases. For instance, exosome contents have been utilized biomarkers body fluids (urine, saliva, serum) to identify cancers, autoimmune diseases, inflammatory conditions sepsis. Due their size ability reach tumor microenvironments, exosomes also used carriers for chemotherapeutic drugs drug delivery systems. Furthermore, evidence indicates that malignant cells release into microenvironment, influencing immune paracrine manner. Additionally, cell-derived exosomes, those from Natural Killer (NK) or cytotoxic T lymphocytes (CTLs), show potential therapeutic agents treating malignancies like leukemia. This review discusses diagnostic hematological explores these

Language: Английский

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Targeting the PD-1/PD-L1 Signaling Pathway for Cancer Therapy: Focus on Biomarkers

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1235 - 1235

Published: Jan. 31, 2025

The PD1/PD-L1 axis plays an important immunosuppressive role during the T-cell-mediated immune response, which is essential for physiological homeostasis of system. biology immunological microenvironment extremely complex and crucial development treatment strategies immunotherapy. Characterization immunological, genomic or transcriptomic landscape cancer patients could allow discrimination between responders non-responders to anti-PD-1/PD-L1 therapy. Immune checkpoint inhibitor (ICI) therapy has shown remarkable efficacy in a variety malignancies landmark trials fundamentally changed Current research focuses on maximize patient selection therapy, clarify mechanisms resistance, improve existing biomarkers, including PD-L1 expression tumor mutational burden (TMB), discover new biomarkers. In this review, we focus function PD-1/PD-L1 signaling pathway discuss genomic, epigenetic receiving Finally, provide overview clinical testing antibodies against PD-1/PD-L1.

Language: Английский

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The role of exosomes in liquid biopsy for cancer diagnosis and prognosis prediction

International Journal of Cancer, Journal Year: 2020, Volume and Issue: 148(11), P. 2640 - 2651

Published: Nov. 12, 2020

Abstract Liquid biopsy is a revolutionary strategy in cancer diagnosis and prognosis prediction, which used to analyze cells or cancer‐derived products through biofluids such as blood, urine so on. Exosomes play crucial role mediating cell communication. A growing number of studies have reported that exosomes are involved tumorigenesis, tumor growth, metastasis drug resistance by delivering cargos including nucleic acids protein. Thus, exosomes, new type liquid biopsy, the potential be diagnostic prognostic biomarkers. Herein, we elaborate on current methods introduce novel techniques for exosome isolation characterization. Moreover, elucidate advantages compared other biological components summarize different exosomal biomarkers prediction.

Language: Английский

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Roles of tumor-associated macrophages in tumor progression: implications on therapeutic strategies

Experimental Hematology and Oncology, Journal Year: 2021, Volume and Issue: 10(1)

Published: Dec. 29, 2021

Abstract Macrophages are heterogeneous cells that present as different functional phenotypes due to their plasticity. They can be classified into two categories, namely M1- and M2-like macrophages, which involved in processes diverse anti-tumor activity immunosuppressive tumor promotion. Tumor-associated macrophages (TAMs) defined being of an M2-type considered the active component microenvironment. TAMs multiple progression through expression cytokines, chemokines, growth factors, protein hydrolases more, lead enhance cell proliferation, angiogenesis, immunosuppression, turn supports invasion metastasis. It is assumed abundance major solid tumors correlated a negative patient prognosis. Because currently available data TAMs’ role development, these have emerged promising target for novel cancer treatment strategies. In this paper, we will briefly describe origins types try comprehensively show how contribute tumorigenesis disease progression. Finally, main TAM-based therapeutic strategies available.

Language: Английский

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