Mouse Type-I Interferon-Mannosylated Albumin Fusion Protein for the Treatment of Chronic Hepatitis DOI Creative Commons
Yuki Minayoshi, Hitoshi Maeda,

Keisuke Hamasaki

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(2), P. 260 - 260

Published: Feb. 19, 2024

Although a lot of effort has been put into creating drugs and combination therapies against chronic hepatitis, no effective treatment established. Type-I interferon is promising therapeutic for hepatitis due to its excellent anti-inflammatory effects through receptors on hepatic macrophages. To develop type-I IFN equipped with the ability target macrophages macrophage mannose receptor, present study designed mouse interferon-mannosylated albumin fusion protein using site-specific mutagenesis technology. This exhibited induction molecules, such as IL-10, IL-1Ra, PD-1, in RAW264.7 cells, or hepatoprotective carbon tetrachloride-induced mice. As expected, biological actions were significantly superior those human proteins. Furthermore, repeated administration mice clearly suppressed area liver fibrosis hydroxyproline contents, not only reduction levels inflammatory cytokine (TNF-α) fibrosis-related genes (TGF-β, Fibronectin, Snail, Collagen 1α2), but also shift phenotype from anti-inflammatory. Therefore, potential new agent hepatitis.

Language: Английский

Targeting cytokine and chemokine signaling pathways for cancer therapy DOI Creative Commons
Ming Yi, Tianye Li,

Mengke Niu

et al.

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

Published: July 22, 2024

Abstract Cytokines are critical in regulating immune responses and cellular behavior, playing dual roles both normal physiology the pathology of diseases such as cancer. These molecules, including interleukins, interferons, tumor necrosis factors, chemokines, growth factors like TGF-β, VEGF, EGF, can promote or inhibit growth, influence microenvironment, impact efficacy cancer treatments. Recent advances targeting these pathways have shown promising therapeutic potential, offering new strategies to modulate system, progression, overcome resistance conventional therapies. In this review, we summarized current understanding implications cytokine chemokine signaling By exploring molecules biology response, highlighted development novel agents aimed at modulating combat The review elaborated on nature cytokines promoters suppressors tumorigenesis, depending context, discussed challenges opportunities presents for intervention. We also examined latest advancements targeted therapies, monoclonal antibodies, bispecific receptor inhibitors, fusion proteins, engineered variants, their metastasis, microenvironment. Additionally, evaluated potential combining therapies with other treatment modalities improve patient outcomes. Besides, focused ongoing research clinical trials that pivotal advancing our application cytokine- chemokine-targeted patients.

Language: Английский

Citations

60
cGAS-STING pathway mediates activation of dendritic cell sensing of immunogenic tumors DOI Creative Commons

Guohao Li,

Xiangqian Zhao,

Zuda Zheng

et al.

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: March 21, 2024

Abstract Type I interferons (IFN-I) play pivotal roles in tumor therapy for three decades, underscoring the critical importance of maintaining integrity IFN-1 signaling pathway radiotherapy, chemotherapy, targeted therapy, and immunotherapy. However, specific mechanism by which IFN-I contributes to these therapies, particularly terms activating dendritic cells (DCs), remains unclear. Based on recent studies, aberrant DNA cytoplasm activates cyclic GMP-AMP synthase (cGAS)- stimulator interferon genes (STING) pathway, turn produces IFN-I, is essential antiviral anticancer immunity. Notably, STING can also enhance immunity promoting autophagy, inflammation, glycolysis an IFN-I-independent manner. These research advancements contribute our comprehension distinctions between drugs agonists context oncology shed light challenges involved developing agonist drugs. Thus, we aimed summarize novel mechanisms underlying cGAS-STING-IFN-I signal activation DC-mediated antigen presentation its role cancer immune cycle this review.

Language: Английский

Citations

19
Emerging role of immunogenic cell death in cancer immunotherapy: Advancing next-generation CAR-T cell immunotherapy by combination DOI
Zhaokai Zhou, Yumiao Mai, Ge Zhang

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 598, P. 217079 - 217079

Published: June 25, 2024

Language: Английский

Citations

12
Metabolic adaptations determine whether natural killer cells fail or thrive within the tumor microenvironment DOI

Adnan Moinuddin,

Sophie M. Poznanski, Ana L. Portillo

et al.

Immunological Reviews, Journal Year: 2024, Volume and Issue: 323(1), P. 19 - 39

Published: March 9, 2024

Summary Natural Killer (NK) cells are a top contender in the development of adoptive cell therapies for cancer due to their diverse antitumor functions and ability restrict activation against nonmalignant cells. Despite success hematologic malignancies, NK cell‐based have been limited context solid tumors. Tumor undergo various metabolic adaptations sustain immense energy demands that needed support rapid uncontrolled proliferation. As result, tumor microenvironment (TME) is depleted nutrients fuel immune activity contains several immunosuppressive metabolites hinder functions. Further, we now know status main determining factor effector Hence, withstand adapt these metabolically hostile conditions imperative effective sustained TME. With this mind, review consequences hostility TME on metabolism function. We also discuss tumor‐like programs induced by STAT3‐mediated expansion thrive Finally, examine how other approaches can be applied enhance

Language: Английский

Citations

8
Metabolic reprograming mediated by tumor cell-intrinsic type I IFN signaling is required for CD47-SIRPα blockade efficacy DOI Creative Commons
Hang Zhou, Wenjun Wang, Hairong Xu

et al.

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

Published: July 9, 2024

Abstract Type I interferons have been well recognized for their roles in various types of immune cells during tumor immunotherapy. However, direct effects on are less understood. Oxidative phosphorylation is typically latent cells. Whether oxidative can be targeted immunotherapy remains unclear. Here, we find that cell responsiveness to type I, but not II interferons, essential CD47-SIRPα blockade female mice. Mechanistically, directly reprogram metabolism by activating ATP production an ISG15-dependent manner. extracellular release also promoted due enhanced secretory autophagy. Functionally, with genetic deficiency or autophagy resistant blockade. released upon required antitumor T response induction via P2X7 receptor-mediated dendritic activation. Based this mechanism, combinations inhibitors ATP-degrading ectoenzymes, CD39 and CD73, designed show synergistic Together, these data reveal important role metabolic reprograming provide rational strategies harnessing mechanism efficacy

Language: Английский

Citations

7
Plasmacytoid dendritic cells at the forefront of anti-cancer immunity: rewiring strategies for tumor microenvironment remodeling DOI Creative Commons
Matilde Monti,

Giorgia Ferrari,

Luisa Gazzurelli

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: July 17, 2024

Abstract Plasmacytoid dendritic cells (pDCs) are multifaceted immune executing various innate immunological functions. Their first line of defence consists in type I interferons (I-IFN) production upon nucleic acids sensing through endosomal Toll-like receptor (TLR) 7- and 9-dependent signalling pathways. Type IFNs a class proinflammatory cytokines that have context-dependent functions on cancer immunosurveillance immunoediting. In the last few years, different studies reported pDCs also able to sense cytosolic DNA cGAS–STING (stimulator interferon genes) pathway eliciting potent I-IFN independently TLR7/9. Human endowed with direct effector via upregulation TRAIL granzyme B, latter modulated by abundant tissues. been detected wide variety human malignant neoplasms, including virus-associated cancers, recruited chemotactic stimuli. Although role surveillance is still uncompletely understood, their spontaneous activation has rarely documented; moreover, presence tumor microenvironment (TME) associated tolerogenic phenotype induced immunosuppressive or oncometabolites. Currently tested treatment options can lead disruption TME, providing relevant clinical benefit. On contrary, antibody–drug conjugates targeting BDCA-2 tumor-associated (TA-pDCs) could be proposed as novel immunomodulatory therapies achieve disease control patients advance stage hematologic malignancies solid tumors. This Review integrate recent evidence biology pharmacological modulation, suggesting at forefront immunity.

Language: Английский

Citations

5
GBM immunotherapy: Exploring molecular and clinical frontiers DOI
Mrinal K. Ghosh,

Sunny Kumar,

Sabana Begam

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 356, P. 123018 - 123018

Published: Aug. 28, 2024

Language: Английский

Citations

5
Environment-responsive dendrobium polysaccharide hydrogel embedding manganese microsphere as a post-operative adjuvant to boost cascaded immune cycle against melanoma DOI Creative Commons
Nan Gao, Yiran Huang,

Shisuo Jing

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(10), P. 3810 - 3826

Published: Jan. 1, 2024

Surgical resection is a primary treatment for solid tumors, but high rates of tumor recurrence and metastasis post-surgery present significant challenges. Manganese (Mn

Language: Английский

Citations

4
TAGLN2 induces resistance signature ISGs by activating AKT-YBX1 signal with dual pathways and mediates the IFN-related DNA damage resistance in gastric cancer DOI Creative Commons
Huiqin Zhuo, Jingjing Hou, Zhijun Hong

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(8)

Published: Aug. 21, 2024

Abstract Recently, various cancer types have been identified to express a distinct subset of Interferon-stimulated genes (ISGs) that mediate therapy resistance. The mechanism through which cells maintain prolonged Interferon stimulation effects coordinate resistance remains unclear. Our research demonstrated aberrant upregulation TAGLN2 is associated with gastric progression, and inhibiting its expression renders more susceptible chemotherapy radiation. We uncovered novel role for in the signature ISGs by enhancing YBX1-associated ssDNA aggregation cGAS-STING pathway activation. modulates YBX1 recruiting c-Myc SOX9 promoter region directly interacting AKT-YBX1, thereby phosphorylation nuclear translocation. Significantly, targeted downregulation key proteins, inhibition TAGLN2-YBX1-AKT interaction (using Fisetin or MK2206) disruption substantially reduced accumulation, subsequent upregulation, combination Cisplatin MK2206 displayed synergistic effect higher -expressing xenograft tumors. Clinical analysis indicated derived nine-gene set effectively predicts therapeutic sensitivity long-term prognosis patients. These findings suggest TAGLN2, induced are predictive markers clinical outcomes, targeting this axis an attractive sensitization strategy.

Language: Английский

Citations

4
The danger theory of immunity revisited DOI
Guido Kroemer, Léa Montégut, Oliver Kepp

et al.

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: 24(12), P. 912 - 928

Published: Nov. 7, 2024

Language: Английский

Citations

4