Advances in dendritic cell vaccination therapy of cancer

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 164, P. 114954 - 114954

Published: May 29, 2023

Traditionally, vaccines have helped eradication of several infectious diseases and also saved millions lives in the human history. Those prophylactic acted through inducing immune responses against a live attenuated, killed organism or antigenic subunits to protect recipient real infection caused by pathogenic microorganism. Nevertheless, development anticancer as valuable targets health has faced challenges requires further optimizations. Dendritic cells (DCs) are most potent antigen presenting (APCs) that play essential roles tumor immunotherapies induction CD8+ T cell immunity. Accordingly, various strategies been tested employ DCs therapeutic for exploiting their activity cells. Application whole purified/recombinant peptides common approaches pulsing DCs, which then injected back into patients. Although some hopeful results reported number DC animal clinical trials cancer patients, such still inefficient require optimization. Failure vaccination is postulated due immunosuppressive microenvironment (TME), overexpression checkpoint proteins, suboptimal avidity tumor-associated (TAA)-specific lymphocytes, lack appropriate adjuvants. In this review, we an overview current experiments evaluated efficacy well focusing on improve potential including combination therapy with inhibitors (ICIs).

Language: Английский

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Cancer stem cells in immunoregulation and bypassing anti-checkpoint therapy

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 156, P. 113906 - 113906

Published: Oct. 25, 2022

Tumor microenvironment (TME) takes critical roles in tumor resistance to immune checkpoint inhibitors (ICIs) including anti-programmed death-1 (PD-1) or death-ligand 1 (PD-L1). Cancer stem cells (CSCs) are one of the key components TME that play important immunoregulation and therapy resistance. CSCs suppress CD8+ T cell infiltration, promote recruitment type 2 macrophages (M2) activity neutrophils (N2). There is a positive association between CSC expansion with high PD-L1 expression TME, higher than cancer cells. metastatic induces dedifferentiation program through stimulating an epithelial-mesenchymal transition (EMT) profile, thereby replenishing proportion inside tumor. Conversion from EMT mesenchymal-epithelial (MET) downregulates on non-CSCs increases ICI efficacy. evidence replenishment secondary anti-PD-1 therapy. Targeting is, fact, step effective breakdown reducing recurrence after immunotherapy. A number signaling involved enrichment within area, among them focus over transforming growth factor-β (TGF-β). TGF-β program, its as bridge increased level rationalizes application dual TGF-β/anti-PD-L1 strategy for reinvigorating immunoactivities patients under In this review, we aimed discuss about connections ecosystem impact such interactions responses

Language: Английский

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Lipid nanoparticle-based mRNA delivery systems for cancer immunotherapy

Nano Convergence, Journal Year: 2023, Volume and Issue: 10(1)

Published: Aug. 7, 2023

Abstract Cancer immunotherapy, which harnesses the power of immune system, has shown immense promise in fight against malignancies. Messenger RNA (mRNA) stands as a versatile instrument this context, with its capacity to encode tumor-associated antigens (TAAs), cell receptors, cytokines, and antibodies. Nevertheless, inherent structural instability mRNA requires development effective delivery systems. Lipid nanoparticles (LNPs) have emerged significant candidates for cancer providing both protection enhanced intracellular efficiency. In review, we offer comprehensive summary recent advancements LNP-based systems, focus on strategies optimizing design mRNA-encoded therapeutics treatment. Furthermore, delve into challenges encountered field contemplate future perspectives, aiming improve safety efficacy immunotherapies. Graphical

Language: Английский

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B7-H3 immunoregulatory roles in cancer

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 163, P. 114890 - 114890

Published: May 15, 2023

B7 homolog 3 (B7-H3, also called CD276) is a checkpoint of family that aberrantly and consistently expressed in several human cancers, its overexpression correlates with weak prognosis. B7-H3 on number cells, it acts as driver immune evasion. This mediated through hampering T cell infiltration promoting exhaustion CD8+ cells. Increased activity promotes macrophage polarity toward pro-tumor type 2 (M2) phenotype. In addition, high induces aberrant angiogenesis to promote hypoxia, result which resistance common inhibitor (ICI) therapy. the impact hypoxia dampening recruitment into tumor area. The immunosuppressive property offers insights targeting this desired approach cancer immunotherapy. can be target blocking monoclonal antibodies (mAbs), combination therapies, chimeric antigen receptor-modified (CAR-T) cells bispecific antibodies.

Language: Английский

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Extracellular fluid viscosity regulates human mesenchymal stem cell lineage and function

Science Advances, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 1, 2025

Human mesenchymal stem cells (hMSCs) respond to mechanical stimuli, including stiffness and viscoelasticity. To date, it is unknown how extracellular fluid viscosity affects hMSC function on substrates of different While hMSCs assume an adipogenic phenotype gels low prescribed stress relaxation times, elevated sufficient bias toward osteogenic phenotype. Elevated induces Arp2/3-dependent actin remodeling, enhances NHE1 activity, promotes spreading via up-regulation integrin-linked kinase. The resulting increase in membrane tension triggers the activation transient receptor potential cation vanilloid 4 facilitate calcium influx, thereby stimulating RhoA/ROCK driving YAP-dependent RUNX2 translocation nucleus, leading differentiation. soft at relative basal favor M2 macrophage This study establishes as a key physical cue that imprints memory immunosuppressive

Language: Английский

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Inflammation-mediated matrix remodeling of extracellular matrix-mimicking biomaterials in tissue engineering and regenerative medicine

Acta Biomaterialia, Journal Year: 2022, Volume and Issue: 151, P. 106 - 117

Published: Aug. 13, 2022

Language: Английский

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HHLA2 immune-regulatory roles in cancer

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 162, P. 114639 - 114639

Published: April 1, 2023

Human endogenous retrovirus H long terminal repeat-associating protein 2 (HHLA2 or B7-H7) is a newly discovered B7 family member. HHLA2 aberrantly expressed in solid tumors and exerts co-stimulatory co-inhibitory activities dependent on interaction with counter receptors. represents effects upon transmembrane immunoglobulin domain containing (TMIGD2, also called CD28H), but its killer cell Ig-like receptor, three Ig domains cytoplasmic tail 3 (KIR3DL3) renders effects. TMIGD2 mainly resting naïve T cells, whereas expression of KIR3DL3 occurs activated cells. HHLA2/KIR3DL3 attenuates responses from both innate adaptive anti-tumor immunity, the activity within this axis regarded as biomarker weak prognosis cancer patients. promotes CD8+ exhaustion induces macrophage polarity toward pro-tumor M2 phenotype. diverse profile tumor stroma. Tumoral presumably higher compared programmed death-ligand 1 (PD-L1), co-expression PD-L1 indicative more severe outcomes. A suggested strategy patients HHLA2high to use monoclonal antibodies for specifically suppressing inhibitory receptor KIR3DL3, not ligand. can be target development agonistic bispecific hampering resistance death-1 (PD-1)/PD-L1 blockade therapy.

Language: Английский

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Long Non-Coding RNAs in Colorectal Cancer: Navigating the Intersections of Immunity, Intercellular Communication, and Therapeutic Potential

Biomedicines, Journal Year: 2023, Volume and Issue: 11(9), P. 2411 - 2411

Published: Aug. 28, 2023

This comprehensive review elucidates the intricate roles of long non-coding RNAs (lncRNAs) within colorectal cancer (CRC) microenvironment, intersecting domains immunity, intercellular communication, and therapeutic potential. lncRNAs, which are significantly involved in pathogenesis CRC, immune evasion, treatment response to have crucial implications inflammation serve as promising candidates for novel strategies biomarkers. scrutinizes interaction lncRNAs with Consensus Molecular Subtypes (CMSs) their complex interplay tumor stroma affecting immunity inflammation, conveyance via extracellular vesicles, particularly exosomes. Furthermore, we delve into relationship between other RNAs, including microRNAs circular mediating cell-to-cell communication CRC microenvironment. Lastly, propose potential manipulate enhance anti-tumor thereby underlining significance devising innovative interventions CRC.

Language: Английский

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Immunosuppressive effects of morphine on macrophage polarization and function

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 975, P. 176637 - 176637

Published: May 8, 2024

Language: Английский

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Hypoxic tumor-derived exosomal miR-4488 induces macrophage M2 polarization to promote liver metastasis of pancreatic neuroendocrine neoplasm through RTN3/FABP5 mediated fatty acid oxidation

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(8), P. 3201 - 3218

Published: Jan. 1, 2024

Tumor-associated macrophages (TAMs) represent a predominant cellular component within the tumor microenvironment (TME) of pancreatic neuroendocrine neoplasms (pNENs). There is growing body evidence highlighting critical role exosomes in facilitating communication between cells and TAMs, thereby contributing to establishment premetastatic niche. Nonetheless, specific mechanisms through which derived from influence macrophage polarization under hypoxic conditions pNENs, manner these interactions support cancer metastasis, remain largely unexplored. Recognizing capacity transfer miRNAs that can modify behaviors, our research identified significant overexpression miR-4488 pNEN cells. Furthermore, we observed absorbed circulating exosomal underwent M2-like polarization. Our investigations revealed promotes by directly targeting suppressing RTN3 macrophages. This suppression enhances fatty acid oxidation activates PI3K/AKT/mTOR signaling pathway interaction downregulation FABP5. Additionally, M2 polarized contribute formation niche advance pNENs metastasis releasing MMP2, establishing positive feedback loop involving miR-4488, RTN3, FABP5, MMP2 Together, findings shed light on mediating intrahepatic macrophages, suggesting holds potential as valuable biomarker therapeutic target for pNENs.

Language: Английский

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