Immune Checkpoint Inhibitors in Cancer Therapy

Current Oncology, Journal Year: 2022, Volume and Issue: 29(5), P. 3044 - 3060

Published: April 24, 2022

The discovery of immune checkpoint proteins such as PD-1/PDL-1 and CTLA-4 represents a significant breakthrough in the field cancer immunotherapy. Therefore, humanized monoclonal antibodies, targeting these have been utilized successfully patients with metastatic melanoma, renal cell carcinoma, head neck cancers non-small lung cancer. US FDA has approved three different categories inhibitors (ICIs) PD-1 (Nivolumab, Pembrolizumab, Cemiplimab), PDL-1 (Atezolimumab, Durvalumab Avelumab), inhibitor (Ipilimumab). Unfortunately, not all respond favourably to drugs, highlighting role biomarkers Tumour mutation burden (TMB), expression, microbiome, hypoxia, interferon-γ, ECM predicting responses ICIs-based current study aims review literature updates on ICIs therapy.

Language: Английский

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Tumor microenvironment: barrier or opportunity towards effective cancer therapy

Journal of Biomedical Science, Journal Year: 2022, Volume and Issue: 29(1)

Published: Oct. 17, 2022

Abstract Tumor microenvironment (TME) is a specialized ecosystem of host components, designed by tumor cells for successful development and metastasis tumor. With the advent 3D culture advanced bioinformatic methodologies, it now possible to study TME’s individual components their interplay at higher resolution. Deeper understanding immune cell’s diversity, stromal constituents, repertoire profiling, neoantigen prediction TMEs has provided opportunity explore spatial temporal regulation therapeutic interventions. The variation TME composition among patients plays an important role in determining responders non-responders towards cancer immunotherapy. Therefore, there could be possibility reprogramming overcome widely prevailing issue immunotherapeutic resistance. focus present review understand complexity comprehending future perspective its as potential targets. later part describes sophisticated models emerging valuable means extensive account tools profile predict neoantigens. Overall, this provides comprehensive current knowledge available target TME.

Language: Английский

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Targeting the tumor stroma for cancer therapy

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Nov. 2, 2022

Tumors are comprised of both cancer cells and surrounding stromal components. As an essential part the tumor microenvironment, stroma is highly dynamic, heterogeneous commonly tumor-type specific, it mainly includes noncellular compositions such as extracellular matrix unique cancer-associated vascular system well a wide variety cellular components including activated fibroblasts, mesenchymal cells, pericytes. All these elements operate with each other in coordinated fashion collectively promote initiation, progression, metastasis therapeutic resistance. Over past few decades, numerous studies have been conducted to study interaction crosstalk between neoplastic cells. Meanwhile, we also witnessed exponential increase investigation recognition critical roles solid tumors. A series clinical trials targeting launched continually. In this review, introduce discuss current advances understanding various their cancers. We elaborate on potential novel approaches for tumor-stroma-based targeting, aim leap from bench bedside.

Language: Английский

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Recent advances in overcoming barriers to cell‐based delivery systems for cancer immunotherapy

Exploration, Journal Year: 2022, Volume and Issue: 2(3)

Published: March 15, 2022

Immunotherapy strategies that use cell-based delivery systems have sparked much interest in the treatment of malignancies, owing to their high biocompatibility, excellent tumor targeting capability, and unique biofunctionalities growth process. A variety design principles for immunotherapy, including cell surface decoration, membrane coating, encapsulation, genetically engineered cell, cell-derived exosomes, give cancer immunotherapy great potential improve therapeutic efficacy reduce adverse effects. However, methods is still limited, practical uses are hampered due complex physiological immunological obstacles, such as physical barriers immune infiltration, immunosuppressive microenvironment, upregulation pathways, metabolic restriction. In this review, we present an overview maximize impact, along with anatomical, metabolic, impediments using treat cancer. Following that, a summary novel been created overcome these obstacles immunotherapeutic provided. Also, prospects next-step development concluded end.

Language: Английский

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Tumor microenvironment signaling and therapeutics in cancer progression

Cancer Communications, Journal Year: 2023, Volume and Issue: 43(5), P. 525 - 561

Published: April 2, 2023

Abstract Tumor development and metastasis are facilitated by the complex interactions between cancer cells their microenvironment, which comprises stromal extracellular matrix (ECM) components, among other factors. Stromal can adopt new phenotypes to promote tumor cell invasion. A deep understanding of signaling pathways involved in cell‐to‐cell cell‐to‐ECM is needed design effective intervention strategies that might interrupt these interactions. In this review, we describe microenvironment (TME) components associated therapeutics. We discuss clinical advances prevalent newly discovered TME, immune checkpoints immunosuppressive chemokines, currently used inhibitors targeting pathways. These include both intrinsic non‐autonomous TME: protein kinase C (PKC) signaling, Notch, transforming growth factor (TGF‐β) Endoplasmic Reticulum (ER) stress response, lactate Metabolic reprogramming, cyclic GMP–AMP synthase (cGAS)–stimulator interferon genes (STING) Siglec also recent Programmed Cell Death Protein 1 (PD‐1), Cytotoxic T‐Lymphocyte Associated 4 (CTLA4), T‐cell immunoglobulin mucin‐3 (TIM‐3) Lymphocyte Activating Gene 3 (LAG3) checkpoint along with C‐C chemokine receptor (CCR4)‐ class chemokines 22 (CCL22)/ 17 (CCL17), type 2 (CCR2)‐ (C‐C motif) ligand (CCL2), 5 (CCR5)‐ (CCL3) axis TME. addition, review provides a holistic TME as three‐dimensional microfluidic models believed recapitulate original characteristics patient hence may be platform study mechanisms screen for various anti‐cancer therapies. further systemic influences gut microbiota reprogramming treatment response. Overall, comprehensive analysis diverse most critical highlighting newest preclinical studies underlying biology. highlight importance technologies microfluidics lab‐on‐chip research present an overview extrinsic factors, such inhabitant human microbiome, have potential modulate biology drug responses.

Language: Английский

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Extracellular Vesicles: New Classification and Tumor Immunosuppression

Biology, Journal Year: 2023, Volume and Issue: 12(1), P. 110 - 110

Published: Jan. 10, 2023

Extracellular vesicles (EVs) are cell-derived membrane-surrounded carrying various types of molecules. These EV cargoes often used as pathophysiological biomarkers and delivered to recipient cells whose fates altered in local distant tissues. Classical EVs exosomes, microvesicles, apoptotic bodies, while recent studies discovered autophagic EVs, stressed matrix vesicles. Here, we classify classical new non-EV nanoparticles. We also review EVs-mediated intercellular communication between cancer tumor-associated cells, such cancer-associated fibroblasts, adipocytes, blood vessels, lymphatic immune cells. Of note, play crucial roles immunosuppression, evasion, immunotherapy resistance. Thus, change hot tumors into cold ones. Moreover, affect nonimmune promote cellular transformation, including epithelial-to-mesenchymal transition (EMT), chemoresistance, tumor production, destruction biological barriers, angiogenesis, lymphangiogenesis, metastatic niche formation.

Language: Английский

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The Molecular Interaction of Collagen with Cell Receptors for Biological Function

Polymers, Journal Year: 2022, Volume and Issue: 14(5), P. 876 - 876

Published: Feb. 23, 2022

Collagen, an extracellular protein, covers the entire human body and has several important biological functions in normal physiology. Recently, collagen from non-human sources attracted attention for therapeutic management biomedical applications. In this regard, both land-based animals such as cow, pig, chicken, camel, sheep, marine-based resources fish, octopus, starfish, sea-cucumber, jellyfish are widely used extraction. The extracted is transformed into peptides, hydrolysates, films, hydrogels, scaffolds, sponges 3D matrix food addition, many strategic ideas continuously emerging to develop innovative advanced biomaterials. For purpose, it understand fundamental perception of how communicates with receptors cells trigger cell signaling pathways. Therefore, review discloses molecular interaction receptor molecules carry out cellular By understanding actual mechanism, opens up new concepts next level research

Language: Английский

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Modulating extracellular matrix stiffness: a strategic approach to boost cancer immunotherapy

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(5)

Published: May 1, 2024

Abstract The interplay between extracellular matrix (ECM) stiffness and the tumor microenvironment is increasingly recognized as a critical factor in cancer progression efficacy of immunotherapy. This review comprehensively discusses key factors regulating ECM remodeling, including activation cancer-associated fibroblasts accumulation crosslinking proteins. Furthermore, it provides detailed exploration how influences behaviors both immune cells. Significantly, impact on response to various immunotherapy strategies, such checkpoint blockade, adoptive cell therapy, oncolytic virus therapeutic vaccines, thoroughly examined. also addresses challenges translating research findings into clinical practice, highlighting need for more precise biomaterials that accurately mimic development novel strategies. insights offered aim guide future research, with potential enhance effectiveness modalities.

Language: Английский

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Extracellular‐Vesicle‐Based Drug Delivery Systems for Enhanced Antitumor Therapies through Modulating the Cancer‐Immunity Cycle

Advanced Materials, Journal Year: 2022, Volume and Issue: 34(52)

Published: June 21, 2022

Although immunotherapy harnessing activity of the immune system against tumors has made great progress, treatment efficacy remains limited in most cancers. Current anticancer is primarily based on T-cell-mediated cellular immunity, which highly relies efficiency triggering cancer-immunity cycle, namely, tumor antigen release, presentation by presenting cells, T cell activation, recruitment and infiltration cells into tumors, recognition killing cells. Unfortunately, these immunotherapies are restricted inefficient drug delivery acting only a single step cycle. Due to high biocompatibility, low immunogenicity, intrinsic targeting, easy chemical genetic manipulation, extracellular vesicle (EV)-based systems widely used amplify responses serving as an integrated platform for multiple drugs or therapeutic strategies synergistically activate several steps This review summarizes various mechanisms related affecting cycle disorders. Meanwhile, preparation application EV-based modulating introduced, especially improvement tumors. Finally, opportunities challenges translational clinical applications briefly discussed.

Language: Английский

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The Extracellular Matrix: Its Composition, Function, Remodeling, and Role in Tumorigenesis

Biomimetics, Journal Year: 2023, Volume and Issue: 8(2), P. 146 - 146

Published: April 5, 2023

The extracellular matrix (ECM) is a ubiquitous member of the body and key to maintenance tissue organ integrity. Initially thought be bystander in many cellular processes, has been shown have diverse components that regulate activate processes ultimately influence cell phenotype. Importantly, ECM’s composition, architecture, stiffness/elasticity phenotypes. Under normal conditions during development, synthesized ECM constantly undergoes degradation remodeling via action proteases maintain homeostasis. In pathological including fibrosis cancer, synthesis, remodeling, dysregulated, causing its integrity altered. Both physical chemical cues from are sensed receptors integrins play roles driving proliferation differentiation progression various diseases such as cancers. Advances ‘omics’ technologies seen an increase studies focusing on bidirectional cell–matrix interactions, here, we highlight emerging knowledge role played by development conditions. This review summarizes current ECM-targeted therapies can modify tumors overcome drug resistance better cancer treatment.

Language: Английский

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