Immune checkpoint therapy—current perspectives and future directions

Cell, Journal Year: 2023, Volume and Issue: 186(8), P. 1652 - 1669

Published: April 1, 2023

Language: Английский

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The role of PD-1 signaling in health and immune-related diseases

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 16, 2023

Programmed cell death 1 receptor (PD-1) and its ligands constitute an inhibitory pathway to mediate the mechanism of immune tolerance provide homeostasis. Significantly, binding partners PD-1 associated are diverse, which facilitates immunosuppression in cooperation with other checkpoint proteins. Accumulating evidence has demonstrated important immunosuppressive role axis tumor microenvironment autoimmune diseases. In addition, blockades have been approved treat various cancers, including solid tumors hematological malignancies. Here, we a comprehensive review pathway, focusing on structure expression PD-1, programmed ligand (PD-L1), 2 (PD-L2); diverse biological functions signaling health immune-related diseases (including immunity, autoimmunity, infectious transplantation allergy privilege); adverse events related PD-L1 inhibitors.

Language: Английский

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The role of tumor-associated macrophages in tumor immune evasion

Journal of Cancer Research and Clinical Oncology, Journal Year: 2024, Volume and Issue: 150(5)

Published: May 7, 2024

Abstract Background Tumor growth is closely linked to the activities of various cells in tumor microenvironment (TME), particularly immune cells. During progression, circulating monocytes and macrophages are recruited, altering TME accelerating growth. These adjust their functions response signals from stromal Tumor-associated (TAMs), similar M2 macrophages, key regulators TME. Methods We review origins, characteristics, TAMs within This analysis includes mechanisms through which facilitate evasion promote metastasis. Additionally, we explore potential therapeutic strategies that target TAMs. Results instrumental mediating malignant behaviors. They release cytokines inhibit effector attract additional immunosuppressive primarily T cells, inducing exhaustion directly, influencing activity indirectly cellular interactions, or suppressing checkpoints. directly involved proliferation, angiogenesis, invasion, Summary Developing innovative tumor-targeted therapies immunotherapeutic currently a promising focus oncology. Given pivotal role evasion, several approaches have been devised them. include leveraging epigenetics, metabolic reprogramming, engineering repolarize TAMs, inhibiting recruitment activity, using as drug delivery vehicles. Although some these remain distant clinical application, believe future targeting will offer significant benefits cancer patients.

Language: Английский

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Benzosceptrin C induces lysosomal degradation of PD-L1 and promotes antitumor immunity by targeting DHHC3

Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(2), P. 101357 - 101357

Published: Jan. 21, 2024

Programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) blockade has become a mainstay of cancer immunotherapy. Targeting the PD-1/PD-L1 axis with small molecules is an attractive approach to enhance antitumor immunity. Here, we identified natural marine product, benzosceptrin C (BC), that enhances cytotoxicity T cells by reducing abundance PD-L1. Furthermore, BC exerts its effect in mice bearing MC38 tumors activating tumor-infiltrating Mechanistic studies suggest can prevent palmitoylation PD-L1 inhibiting DHHC3 enzymatic activity. Subsequently, transferred from membrane cytoplasm and cannot return via recycling endosomes, triggering lysosome-mediated degradation Moreover, combination anti-CTLA4 effectively Our findings reveal previously unrecognized mechanism represent alternative immune checkpoint (ICB) therapeutic strategy efficacy

Language: Английский

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New insights into the role of macrophages in cancer immunotherapy

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

Published: March 28, 2024

Macrophages are the main component of tumor microenvironment, which differentiated from monocytes in blood and play an important role cancer development. Tumor-associated macrophages (TAMs) can promote growth, invasion, metastasis, resistance to anti–programmed death receptor 1 therapy by regulating programmed cell ligand expression interacting with other immune cells microenvironment. However, when activated properly, also anti-tumor enhancing phagocytosis cytotoxicity cells. TAM is associated poor prognosis drug patients treated immunotherapy, indicating that attractive targets for combined treatment. Combination targeting TAMs immunotherapy overcomes achieved excellent results some cancers, may be a promising strategy treatment future. Herein, we review recent findings on development, immunotherapy. We focus mainly macrophage-centered therapy, including strategies deplete reprogram TAMs, represent potential improving efficacy.

Language: Английский

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Advances in the understanding and therapeutic manipulation of cancer immune responsiveness: a Society for Immunotherapy of Cancer (SITC) review

Journal for ImmunoTherapy of Cancer, Journal Year: 2025, Volume and Issue: 13(1), P. e008876 - e008876

Published: Jan. 1, 2025

Cancer immunotherapy-including immune checkpoint inhibition (ICI) and adoptive cell therapy (ACT)-has become a standard, potentially curative treatment for subset of advanced solid liquid tumors. However, most patients with cancer do not benefit from the rapidly evolving improvements in understanding principal mechanisms determining responsiveness (CIR); including patient-specific genetically determined acquired factors, as well intrinsic biology. Though CIR is multifactorial, fundamental concepts are emerging that should be considered design novel therapeutic strategies related clinical studies. Recent advancements approaches to address limitations current treatments discussed here, specific focus on ICI ACT.

Language: Английский

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The Effect of the Gut Microbiota on Systemic and Anti-Tumor Immunity and Response to Systemic Therapy against Cancer

Cancers, Journal Year: 2022, Volume and Issue: 14(15), P. 3563 - 3563

Published: July 22, 2022

Gut microbiota can have opposing functions from pro-tumorigenic to anti-tumorigenic effects. Increasing preclinical and clinical evidence suggests that the intestinal affects cancer patients' response immune checkpoint inhibitors (ICIs) immunotherapy, such as anti-programmed cell death protein 1 (PD-1) its ligand (PD-L1) anti-cytotoxic T lymphocyte-associated 4 (CTLA-4). Microbiota-induced inflammation possibly contributes tumor growth development. Microbiota-derived metabolites also be converted carcinogenic agents related genetic mutations DNA damage in organs colon. However, other attributes of microbiota, greater diversity specific bacterial species their metabolites, are linked better outcomes potentially improved anti-tumor immunity. In addition, intratumoral microbial composition strongly T-cell-mediated cytotoxicity surveillance, adding more complexity cancer-microbiome-immune axis. Despite emerging for activity gut immuno-oncology, fundamental mechanisms not well understood. This review provides an overview underlying by which enhance or suppress responses. Understanding allows design microbiome-specific treatment strategies improve outcome patients undergoing systemic therapy.

Language: Английский

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Radiation-induced PD-L1 expression in tumor and its microenvironment facilitates cancer-immune escape: a narrative review

Annals of Translational Medicine, Journal Year: 2022, Volume and Issue: 10(24), P. 1406 - 1406

Published: Dec. 1, 2022

Background and Objective: Radiotherapy (RT) is one of the fundamental anti-cancer regimens by means inducing in situ tumor vaccination driving a systemic anti-tumor immune response. It can affect microenvironment (TME) components consisting blood vessels, immunocytes, fibroblasts, extracellular matrix (ECM), might subsequently suppress immunity through expression molecules such as programmed death ligand-1 (PD-L1). Immune checkpoint inhibitors (ICIs), especially anti-programmed cell 1 (PD-1)/PD-L1 therapies, have been regarded effective reinvigoration system another major cancer treatment. Experimentally, combination RT ICIs therapy shows greater synergistic effect than either alone. Methods: We performed narrative review literature PubMed database. The research string comprised various combinations "radiotherapy", "programmed death-ligand 1", "microenvironment", "exosome", "myeloid cell", "tumor immunity". database was searched independently two authors. A third reviewer mediated any discordance results screeners. Key Content Findings: upregulates PD-L1 cells, tumor-derived exosomes (TEXs), myeloid-derived suppressor cells (MDSCs), macrophages. signaling pathways correlated to include DNA damage pathway, epidermal growth factor receptor (EGFR) interferon gamma (IFN-γ) cGAS-STING JAK/STATs pathway. Conclusions: upregulation post-RT found not only but also TME mechanisms evasion. Therefore, further studies are necessary fully comprehend this biological process. Meanwhile, therapies has shown be effective, novel approaches developed adjuvant therapy.

Language: Английский

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The systemic-level repercussions of cancer-associated inflammation mediators produced in the tumor microenvironment

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 22, 2022

The tumor microenvironment is a dynamic, complex, and redundant network of interactions between tumor, immune, stromal cells. In this intricate environment, cells communicate through membrane–membrane, ligand–receptor, exosome, soluble factors, transporter that govern cell fate. These activate the diverse superfluous signaling pathways involved in promotion progression induce subtle changes functional activity infiltrating immune response participates as selective pressure development. early stages development, exerts anti-tumor activity, whereas during advanced stages, establishes mechanisms to evade response, eliciting chronic inflammation process shows pro-tumor effect. deregulated inflammatory state, addition acting locally, also triggers systemic has repercussions various organs tissues are distant from site, causing emergence symptoms designated paraneoplastic syndromes, which compromise treatment, quality life, survival cancer patients. Considering tumor–host relationship an integral dynamic biological system, generated by communication mechanism among primarily orchestrated different signals, such cytokines, chemokines, growth exosomes, provide with energetic components allow it continue proliferating. review, we aim succinct overview involvement cancer-related at local level throughout development some syndromes their main clinical manifestations. addition, these signals will be discussed based on physiological/biological activities innate adaptive cellular require metabolic reprogramming program for full activation cells; thus, requirements by-products released into considered. impact proinflammatory cytokines liver—as critical organ produces leading markers described date—will summarized. Finally, contribution two myelopoiesis cachexia, discussed.

Language: Английский

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Regulations of Tumor Microenvironment by Prostaglandins

Cancers, Journal Year: 2023, Volume and Issue: 15(12), P. 3090 - 3090

Published: June 7, 2023

Prostaglandins, the bioactive lipids generated from metabolism of arachidonic acid through cyclooxygenases, have potent effects on many constituents tumor microenvironments. In this review, we will describe formation and activities prostaglandins in context microenvironment. We discuss regulation cancer-associated fibroblasts immune by their roles escapes during progression. The review concludes with future perspectives improving efficacy immunotherapy repurposing non-steroid anti-inflammatory drugs other prostaglandin modulators.

Language: Английский

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