Macrophages in immunoregulation and therapeutics

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 22, 2023

Abstract Macrophages exist in various tissues, several body cavities, and around mucosal surfaces are a vital part of the innate immune system for host defense against many pathogens cancers. possess binary M1/M2 macrophage polarization settings, which perform central role an array tasks via intrinsic signal cascades and, therefore, must be precisely regulated. Many crucial questions about signaling modulation yet to uncovered. In addition, clinical importance tumor-associated macrophages is becoming more widely recognized as significant progress has been made understanding their biology. Moreover, they integral tumor microenvironment, playing regulation wide variety processes including angiogenesis, extracellular matrix transformation, cancer cell proliferation, metastasis, immunosuppression, resistance chemotherapeutic checkpoint blockade immunotherapies. Herein, we discuss signaling, mechanical stresses modulation, metabolic pathways, mitochondrial transcriptional, epigenetic regulation. Furthermore, have broadly extended traps essential roles autophagy aging regulating functions. discussed recent advances macrophages-mediated autoimmune diseases tumorigenesis. Lastly, targeted therapy portray prospective targets therapeutic strategies health diseases.

Language: Английский

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Microenvironment-driven metabolic adaptations guiding CD8+ T cell anti-tumor immunity

Immunity, Journal Year: 2023, Volume and Issue: 56(1), P. 32 - 42

Published: Jan. 1, 2023

Language: Английский

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Targeting macrophages in hematological malignancies: recent advances and future directions

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

Published: Aug. 17, 2022

Abstract Emerging evidence indicates that the detection and clearance of cancer cells via phagocytosis induced by innate immune checkpoints play significant roles in tumor-mediated escape. The most well-described are “don’t eat me” signals, including CD47/signal regulatory protein α axis (SIRPα), PD-1/PD-L1 axis, CD24/SIGLEC-10 MHC-I/LILRB1 axis. Molecules have been developed to block these pathways enhance phagocytic activity against tumors. Several clinical studies investigated safety efficacy CD47 blockades, either alone or combination with existing therapy hematological malignancies, myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), lymphoma. However, only a minority patients responses treatments alone. Combining blockades other treatment modalities studies, early results suggesting synergistic therapeutic effect. Targeting macrophages bispecific antibodies being explored blood therapy. Furthermore, reprogramming pro-tumor anti-tumor macrophages, CAR (CAR-M) demonstrate activities. In this review, we elucidated distinct types macrophage-targeted strategies from preclinical experiments trials, outlined potential approaches developed.

Language: Английский

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Biological impact and therapeutic perspective of targeting PI3K/Akt signaling in hepatocellular carcinoma: Promises and Challenges

Pharmacological Research, Journal Year: 2022, Volume and Issue: 187, P. 106553 - 106553

Published: Nov. 16, 2022

Cancer progression results from activation of various signaling networks. Among these, PI3K/Akt contributes to proliferation, invasion, and inhibition apoptosis. Hepatocellular carcinoma (HCC) is a primary liver cancer with high incidence rate, especially in regions prevalence viral hepatitis infection. Autoimmune disorders, diabetes mellitus, obesity, alcohol consumption, inflammation can also lead initiation development HCC. The treatment HCC depends on the identification oncogenic factors that tumor cells develop resistance therapy. present review article focuses role progression. Activation promotes glucose uptake, favors glycolysis increases cell proliferation. It inhibits both apoptosis autophagy while promoting survival. stimulates epithelial-to-mesenchymal transition (EMT) matrix-metalloproteinase (MMP) expression during metastasis. In addition increasing colony formation capacity facilitating spread cells, angiogenesis. Therefore, silencing prevents aggressive behavior. confer drug resistance, particularly sorafenib, decreases radio-sensitivity cells. Anti-cancer agents, like phytochemicals small molecules suppress by limiting Being upregulated tissues clinical samples, be used as biomarker predict patients' response

Language: Английский

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Notch signaling pathway in cancer: from mechanistic insights to targeted therapies

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 27, 2024

Notch signaling, renowned for its role in regulating cell fate, organ development, and tissue homeostasis across metazoans, is highly conserved throughout evolution. The receptor ligands are transmembrane proteins containing epidermal growth factor-like repeat sequences, typically necessitating receptor-ligand interaction to initiate classical signaling transduction. Accumulating evidence indicates that the pathway serves as both an oncogenic factor a tumor suppressor various cancer types. Dysregulation of this promotes epithelial-mesenchymal transition angiogenesis malignancies, closely linked proliferation, invasion, metastasis. Furthermore, contributes maintaining stem-like properties cells, thereby enhancing invasiveness. regulatory metabolic reprogramming microenvironment suggests pivotal involvement balancing suppressive effects. Moreover, implicated conferring chemoresistance cells. Therefore, comprehensive understanding these biological processes crucial developing innovative therapeutic strategies targeting signaling. This review focuses on research progress cancers, providing in-depth insights into potential mechanisms regulation occurrence progression cancer. Additionally, summarizes pharmaceutical clinical trials therapy, aiming offer new human malignancies.

Language: Английский

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Noncoding RNAs as regulators of STAT3 pathway in gastrointestinal cancers: Roles in cancer progression and therapeutic response

Medicinal Research Reviews, Journal Year: 2023, Volume and Issue: 43(5), P. 1263 - 1321

Published: March 23, 2023

Abstract Gastrointestinal (GI) tumors (cancers of the esophagus, gastric, liver, pancreas, colon, and rectum) contribute to a large number deaths worldwide. STAT3 is an oncogenic transcription factor that promotes genes associated with proliferation, antiapoptosis, survival, metastasis. overactivated in many human malignancies including GI which accelerates tumor progression, metastasis, drug resistance. Research recent years demonstrated noncoding RNAs (ncRNAs) play major role regulation signaling pathways pathway. The types endogenous ncRNAs are being extensively studied oncology microRNAs, long RNAs, circular RNAs. These can either be tumor‐promoters or tumor‐suppressors each one them imparts their activity via different mechanisms. pathway also tightly modulated by ncRNAs. In this article, we have elaborated on tumor‐promoting tumors. Subsequently, comprehensively discussed as well suppressor functions mechanism action known modulate cancers.

Language: Английский

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In-situ-sprayed therapeutic hydrogel for oxygen-actuated Janus regulation of postsurgical tumor recurrence/metastasis and wound healing

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 27, 2024

Surgery is the mainstay of treatment modality for malignant melanoma. However, deteriorative hypoxic microenvironment after surgery recognized as a stemming cause tumor recurrence/metastasis and delayed wound healing. Here we design construct sprayable therapeutic hydrogel (HIL@Z/P/H) encapsulating tumor-targeted nanodrug photosynthetic cyanobacteria (PCC 7942) to prevent while promote In postsurgical B16F10 melanoma model in female mice, can disrupt cellular redox homeostasis via photodynamic therapy-induced cascade reactions within cells. Besides, photosynthetically generated O

Language: Английский

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Oxygen‐driven cuproptosis synergizes with radiotherapy to potentiate tumor immunotherapy

Aggregate, Journal Year: 2024, Volume and Issue: 5(3)

Published: Jan. 4, 2024

Abstract The immunological implications of cuproptosis, a form cell death highly sensitive to oxygen presence, remain largely unexplored in the context tumor immunotherapy. Herein, we initially investigate positive correlation between cuproptosis and immunotherapy through bioinformatics analysis. Subsequently, an generator loaded with copper ions ( Cu/AP H‐M) has been constructed, which serves as effective carrier crucially enhances oxygenation microenvironment. Importantly, H‐M‐mediated dual strengthening radiotherapy could not only trigger powerful antitumor immunity related immunogenic by RNA‐sequencing analysis, but also effectively inhibit growth both distal situ low rectal tumors after combined immunotherapy, creating robust immune memory effect. Our work reveals beneficial effects enhanced radio‐immunotherapy elucidates its underlying mechanisms, provides novel approach for synergistic integration radiotherapy, broadening scope cuproptosis‐mediated therapy.

Language: Английский

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Tumor microenvironment responsive nanozymes for multimodal imaging of tumors

Nano TransMed, Journal Year: 2024, Volume and Issue: 3, P. 100032 - 100032

Published: Jan. 29, 2024

Nanozymes exhibit immense potential and promising prospects in the realm of diagnostic imaging tumor therapy, owing to their inherent physicochemical properties enzymatic activities. With further development application nanotechnology, nanozymes are expected become an important tool field medicine, providing new solutions for disease diagnosis treatment. This review provides overview recent studies over past five years on capable responding microenvironment (TME) multimodal imaging, with a focus hypoxia, acid pH, excess GSH ROS. In addition, we present current status several common related contrast agents, such as MRI/CT, MRI/PET, MRI/SPECT, PET/CT. Moreover, some thoughts challenges, future development, clinical translation microenvironment-responsive shared. aims provide up-to-date theranostic nanomedicine reference those who fields, promote progress this interdisciplinary subject, accelerate translation.

Language: Английский

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Therapeutic Targeting of Hypoxia-Inducible Factors in Cancer

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2060 - 2060

Published: Feb. 8, 2024

In the realm of cancer therapeutics, targeting hypoxia-inducible factor (HIF) pathway has emerged as a promising strategy. This study delves into intricate web HIF-associated mechanisms, exploring avenues for future anticancer therapies. Framing investigation within broader context progression and hypoxia response, this article aims to decipher pivotal role played by HIF in regulating genes influencing angiogenesis, cell proliferation, glucose metabolism. Employing diverse approaches such inhibitors, anti-angiogenic therapies, hypoxia-activated prodrugs, research methodologically intervenes at different nodes pathway. Findings showcase efficacy agents like EZN-2968, Minnelide, Acriflavine modulating HIF-1α protein synthesis destabilizing HIF-1, providing preliminary proof mRNA modulation antitumor activity. However, challenges, including toxicity, necessitate continued exploration development, exemplified ongoing clinical trials. concludes emphasizing potential targeted therapies disrupting cancer-related signaling pathways.

Language: Английский

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