A Mesoporous Gold Sensor Unveils Phospho PD-L1 in Extracellular Vesicles as a Proxy for PD-L1 Expression in Lung Cancer Tissue DOI
Karthik Balaji Shanmugasundaram, Emtiaz Ahmed,

Xinzhe Miao

et al.

ACS Sensors, Journal Year: 2024, Volume and Issue: 9(6), P. 3009 - 3016

Published: June 5, 2024

Immune checkpoint inhibitors (ICIs) targeting programmed cell death ligand 1 (PD-L1), or its receptor, PD-1 have improved survival in patients with non-small-cell lung cancer (NSCLC). Assessment of PD-L1 expression requires tissue biopsy fine needle aspiration that are currently used to identify most likely respond single agent anti-PD-1/PD-L1 therapy. However, obtaining sufficient generate a proportion score (TPS) ≥ 50% using immunohistochemistry remains challenge potentially may be overcome by liquid biopsies. This study utilized mesoporous gold sensor (MGS) assay examine the phosphorylation status plasma extracellular vesicles (EV pPD-L1) and levels from NSCLC patient samples their association tumor TPS. The 3-dimensional network electrodes provides large surface area, high signal-to-noise ratio, superior electro-conductive framework, thereby significantly improving detection sensitivity nanosensing. Test (

Language: Английский

Tumor microenvironment signaling and therapeutics in cancer progression DOI Creative Commons
Anshika Goenka, Fatima Khan, Bhupender Verma

et al.

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

Citations

122
Radiation-induced PD-L1 expression in tumor and its microenvironment facilitates cancer-immune escape: a narrative review DOI Open Access

Nuo-Han Wang,

Zheng Lei,

Hao-Nan Yang

et al.

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

Citations

45
Tumor-derived exosomes in the cancer immune microenvironment and cancer immunotherapy DOI

Qiushi Tang,

Shuo Yang, Guangpeng He

et al.

Cancer Letters, Journal Year: 2022, Volume and Issue: 548, P. 215823 - 215823

Published: July 12, 2022

Language: Английский

Citations

44
Engineered EVs designed to target diseases of the CNS DOI Creative Commons
Lisa Nieland,

Shadi Mahjoum,

Emily Grandell

et al.

Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 356, P. 493 - 506

Published: March 15, 2023

Diseases of the central nervous system (CNS) are challenging to treat, mainly due blood-brain barrier (BBB), which restricts drugs in circulation from entering target regions brain. To address this issue extracellular vesicles (EVs) have gained increasing scientific interest as carriers able cross BBB with multiplex cargos. EVs secreted by virtually every cell, and their escorted biomolecules part an intercellular information gateway between cells within brain other organs. Scientists undertaken efforts safeguard inherent features therapeutic delivery vehicles, such protecting transferring functional cargo, well loading them small molecules, proteins, oligonucleotides targeting specific cell types for treatment CNS diseases. Here, we review current emerging approaches that engineer EV surface cargo improve responses We summarize existing applications engineered a platform diseases, some been evaluated clinically.

Language: Английский

Citations

41
Extracellular vesicles as next generation immunotherapeutics DOI
David W. Greening, Rong Xu,

Anukreity Ale

et al.

Seminars in Cancer Biology, Journal Year: 2023, Volume and Issue: 90, P. 73 - 100

Published: Feb. 10, 2023

Language: Английский

Citations

40
Targeting MYC at the intersection between cancer metabolism and oncoimmunology DOI Creative Commons
Simran Venkatraman, Brinda Balasubramanian, Chanitra Thuwajit

et al.

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

Published: Feb. 8, 2024

MYC activation is a known hallmark of cancer as it governs the gene targets involved in various facets progression. Of interest, oncometabolism through interactions with its partners and cofactors, well immunity via targets. Recent investigations have taken interest characterizing these multi-Omic approaches, to better understand vastness network. several either or oncoimmunology, few them overlap function. Prominent been observed HIF-1α, promoting glucose glutamine metabolism antigen presentation on regulatory T cells, subsequent metabolic reprogramming. This review explores existing knowledge role oncoimmunology. It also unravels how transcription influences cellular facilitate induction pro- anti-tumoral immunity. Moreover, considering significant roles holds development, present study discusses effective direct indirect therapeutic strategies combat MYC-driven

Language: Английский

Citations

11
The Role of Extracellular Vesicles in Metabolic Reprogramming of the Tumor Microenvironment DOI Creative Commons
Eran Fridman,

Lana Ginini,

Ziv Gil

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(9), P. 1433 - 1433

Published: April 23, 2022

The tumor microenvironment (TME) includes a network of cancerous and non-cancerous cells, together with associated blood vessels, the extracellular matrix, signaling molecules. TME contributes to cancer progression during various phases tumorigenesis, interactions that take place within have become targets focus in therapy development. Extracellular vesicles (EVs) are known be conveyors genetic material, proteins, lipids TME. One hallmarks is its ability reprogram metabolism sustain cell growth proliferation stringent environment. In this review, we provide an overview EV involvement metabolic reprogramming stromal which favors by enhancing angiogenesis, proliferation, metastasis, treatment resistance, immunoevasion. Targeting communication mechanisms systems utilized TME-EVs opening new frontier therapy.

Language: Английский

Citations

37
Exosomes Derived from Immune Cells: The New Role of Tumor Immune Microenvironment and Tumor Therapy DOI Creative Commons
Shiyang Wang, Yue Shi

International Journal of Nanomedicine, Journal Year: 2022, Volume and Issue: Volume 17, P. 6527 - 6550

Published: Dec. 1, 2022

Abstract: Exosomes are small vesicles secreted by living cells, with a typical lipid bilayer structure. They carry variety of proteins, lipids, RNA and other important information, play an role in the transmission substances information between gradually become marker for early diagnosis many diseases tool drug delivery system. Immune cells part tumor microenvironment, they can affect progression secreting immunoreactive substances. This review focuses on effects various immune cell-derived exosomes different stromal microenvironment. derived from not only reshape pro-inflammatory microenvironment to inhibit progression, but also promote inhibiting killing effect NK CD8 + T or promoting immunosuppressive cells. In addition, we discussed that some (such as DC, M1 macrophages neutrophils) inhibitory after being engineered. Keywords: tumor, exosome, immunity, engineered

Language: Английский

Citations

30
Hypoxia-Driven Changes in Tumor Microenvironment: Insights into Exosome-Mediated Cell Interactions DOI Creative Commons

Churan Wang,

Shun Xu,

Xiao Yang

et al.

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 8211 - 8236

Published: Aug. 1, 2024

Hypoxia, as a prominent feature of the tumor microenvironment, has profound impact on multicomponent changes within this environment. Under hypoxic conditions, malignant phenotype cells, variety cell types well intercellular communication and material exchange, undergo complex alterations. These provide significant prospects for exploring mechanisms development under different microenvironmental conditions devising therapeutic strategies. Exosomes secreted by cells stromal are integral components serving crucial mediators have consequently garnered increasing attention from researchers. This review focuses which promote release exosomes alter their encapsulated contents. It also examines effects derived immune other microenvironment. Additionally, we summarize current research progress potential clinical applications propose future directions in field.

Language: Английский

Citations

7
Extracellular vesicle-cell adhesion molecules in tumours: biofunctions and clinical applications DOI Creative Commons

Weikai Lin,

Jianjun Fang,

Shibo Wei

et al.

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: Sept. 21, 2023

Cell adhesion molecule (CAM) is an umbrella term for several families of molecules, including the cadherin family, integrin selectin immunoglobulin superfamily, and some currently unclassified molecules. Extracellular vesicles (EVs) are important information mediators in cell-to-cell communication. Recent evidence has confirmed that CAMs transported by EVs interact with recipient cells to influence EV distribution vivo regulate multiple cellular processes. This review focuses on loading onto EVs, roles regulating distribution, known possible mechanisms these actions. Moreover, herein, we summarize impacts tumour microenvironment (TME) malignant behaviour (proliferation, metastasis, immune escape, so on). In addition, from standpoint clinical applications, significance challenges using EV-CAMs diagnosis therapy tumours discussed. Finally, considering recent advances understanding EV-CAMs, outline significant this field require urgent attention advance research promote applications EV-CAMs. Video Abstract.

Language: Английский

Citations

14