The JAK-STAT pathway at 30: Much learned, much more to do

Cell, Journal Year: 2022, Volume and Issue: 185(21), P. 3857 - 3876

Published: Oct. 1, 2022

Language: Английский

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PD-1/PD-L1 checkpoint inhibitors in advanced hepatocellular carcinoma immunotherapy

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Dec. 19, 2022

Hepatocellular carcinoma (HCC) has a high prevalence and mortality rate worldwide. Sorafenib monotherapy been the standard of first-line treatment for advanced HCC long time, but there are still many shortcomings. In recent years, with deepening research on tumor immune microenvironment, researchers have begun to explore new approaches in immunotherapy, introduction checkpoint inhibitors brought fundamental changes HCC. Programmed cell death protein 1 (PD-1) is an molecule that plays important role down-regulating system function promoting tolerance. ligand (PDL-1) involved evasion by binding PD-1, resulting failure treatment. Currently, immunotherapy targeting PD-1/PD-L1 axis achieved unprecedented success HCC, it also faces great challenges, its low remission be solved. For most patients pathway not only limiting factor antitumor immunity, blocking enough stimulate effective response; thus, combination therapy may better option. this study, microenvironment were reviewed clarify feasibility anti-PD-1/PD-L1 therapy, series clinical trials summarized verify safety efficacy newly developed Furthermore, we focused hyperprogressive disease drug resistance gain understanding blockade as promising

Language: Английский

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How cancer cells make and respond to interferon-I

Trends in cancer, Journal Year: 2022, Volume and Issue: 9(1), P. 83 - 92

Published: Oct. 8, 2022

Acute exposure of cancer cells to high concentrations type I interferon (IFN-I) drives growth arrest and apoptosis, whereas chronic low provides important prosurvival advantages. Tyrosine-phosphorylated IFN-stimulated gene (ISG) factor 3 (ISGF3) acute deleterious responses IFN-I, unphosphorylated (U-)ISGF3, lacking tyrosine phosphorylation, essential constitutive mechanisms. Surprisingly, programmed cell death-ligand 1 (PD-L1), often expressed on the surfaces tumor well recognized for its importance in inactivating cytotoxic T cells, also has cell-intrinsic protumor activities, including dampening levels IFN-I sustaining expression that benefit tumors. More thorough understanding newly complex roles may lead identification novel therapeutic strategies.

Language: Английский

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Targeting innate immune pathways for cancer immunotherapy

Immunity, Journal Year: 2023, Volume and Issue: 56(10), P. 2206 - 2217

Published: Sept. 12, 2023

Language: Английский

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Targeting cytokine and chemokine signaling pathways for cancer therapy

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

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Interferon-stimulated neutrophils as a predictor of immunotherapy response

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(2), P. 253 - 265.e12

Published: Jan. 4, 2024

Despite the remarkable success of anti-cancer immunotherapy, its effectiveness remains confined to a subset patients—emphasizing importance predictive biomarkers in clinical decision-making and further mechanistic understanding treatment response. Current biomarkers, however, lack power required accurately stratify patients. Here, we identify interferon-stimulated, Ly6Ehi neutrophils as blood-borne biomarker anti-PD1 response mice at baseline. are induced by tumor-intrinsic activation STING (stimulator interferon genes) signaling pathway possess ability directly sensitize otherwise non-responsive tumors therapy, part through IL12b-dependent cytotoxic T cells. By translating our pre-clinical findings cohort patients with non-small cell lung cancer melanoma (n = 109), public data 1440), demonstrate predict immunotherapy humans high accuracy (average AUC ≈ 0.9). Overall, study identifies functionally active for use both humans.

Language: Английский

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Harnessing innate immune pathways for therapeutic advancement in cancer

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

Published: March 25, 2024

Abstract The innate immune pathway is receiving increasing attention in cancer therapy. This ubiquitous across various cell types, not only cells but also adaptive cells, tumor and stromal cells. Agonists targeting the have shown profound changes microenvironment (TME) improved prognosis preclinical studies. However, to date, clinical success of drugs remains limited. Interestingly, recent studies that activation can paradoxically promote progression. uncertainty surrounding therapeutic effectiveness targeted for a critical issue needs immediate investigation. In this review, we observe role demonstrates heterogeneity, linked development stage, status, specific types. We propose within TME, exhibits multidimensional diversity. diversity fundamentally rooted cellular heterogeneity manifested as variety signaling networks. pro-tumor effect essentially reflects suppression classical pathways potential alternative pathways. Refining our understanding tumor’s network employing appropriate strategies enhance ability harness anti-tumor ultimately bridge gap from application.

Language: Английский

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Dysregulation in IFN-γ signaling and response: the barricade to tumor immunotherapy

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 18, 2023

Interferon-gamma (IFN-γ) has been identified as a crucial factor in determining the responsiveness to immunotherapy. Produced primarily by natural killer (NK) and T cells, IFN-γ promotes activation, maturation, proliferation, cytokine expression, effector function immune while simultaneously inducing antigen presentation, growth arrest, apoptosis tumor cells. However, cells can hijack signaling pathway mount resistance: rather than increasing antigenicity succumbing death, acquire stemness characteristics express immunosuppressive molecules defend against antitumor immunity. In this review, we summarize potential mechanisms of resistance occurring at two critical stages: disrupted signal transduction along IFNG/IFNGR/JAK/STAT pathway, or preferential expression specific interferon-stimulated genes (ISGs). Elucidating molecular through which develop help identify promising therapeutic targets improve immunotherapy, with broad application value conjugation targeted, antibody cellular therapies.

Language: Английский

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Pre-metastatic niche: formation, characteristics and therapeutic implication

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

Published: Sept. 25, 2024

Language: Английский

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Understanding Autoimmunity: Mechanisms, Predisposing Factors, and Cytokine Therapies

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7666 - 7666

Published: July 12, 2024

Autoimmunity refers to an organism’s immune response against its own healthy cells, tissues, or components, potentially leading irreversible damage vital organs. Central and peripheral tolerance mechanisms play crucial roles in preventing autoimmunity by eliminating self-reactive T B cells. The disruption of immunological tolerance, characterized the failure these mechanisms, results aberrant activation autoreactive lymphocytes that target self-tissues, culminating pathogenesis autoimmune disorders. Genetic predispositions, environmental exposures, immunoregulatory disturbances synergistically contribute susceptibility initiation pathologies. Within realm therapies for diseases, cytokine have emerged as a specialized strategy, targeting cytokine-mediated regulatory pathways rectify imbalances. Proinflammatory cytokines are key players inducing propagating inflammation, highlighting potential managing conditions. This review discusses etiology current therapeutic approaches, prospects future drug design.

Language: Английский

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