Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)
Published: June 25, 2024
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Language: Английский
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
Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)
Published: June 4, 2024
Abstract Pancreatic cancer is a major cause of cancer-related death, but despondently, the outlook and prognosis for this resistant type tumor have remained grim long time. Currently, it extremely challenging to prevent or detect early enough effective treatment because patients rarely exhibit symptoms there are no reliable indicators detection. Most advanced spreading that difficult treat, treatments like chemotherapy radiotherapy can only slightly prolong their life by few months. Immunotherapy has revolutionized pancreatic cancer, yet its effectiveness limited tumor's immunosuppressive hard-to-reach microenvironment. First, article explains microenvironment highlights wide range immunotherapy options, including therapies involving oncolytic viruses, modified T cells (T-cell receptor [TCR]-engineered chimeric antigen [CAR] T-cell therapy), CAR natural killer cell therapy, cytokine-induced cells, immune checkpoint inhibitors, immunomodulators, vaccines, strategies targeting myeloid in context contemporary knowledge future trends. Lastly, discusses main challenges ahead immunotherapy.
Language: Английский
Citations
36
Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)
Published: Aug. 2, 2024
Abstract Metastasis remains a pivotal characteristic of cancer and is the primary contributor to cancer-associated mortality. Despite its significance, mechanisms governing metastasis are not fully elucidated. Contemporary findings in domain biology have shed light on molecular aspects this intricate process. Tumor cells undergoing invasion engage with other cellular entities proteins en route their destination. Insights into these engagements enhanced our comprehension principles directing movement adaptability metastatic cells. The tumor microenvironment plays role facilitating proliferation by enabling navigate through stromal barriers. Such attributes influenced genetic epigenetic changes occurring surrounding milieu. A profound understanding process’s biological indispensable for devising efficacious therapeutic strategies. This review delves recent developments concerning metastasis-associated genes, important signaling pathways, microenvironment, metabolic processes, peripheral immunity, mechanical forces metastasis. In addition, we combine advances particular emphasis prospect developing effective interventions including most popular immunotherapies nanotechnology combat We also identified limitations current research metastasis, encompassing drug resistance, restricted animal models, inadequate biomarkers early detection methods, as well heterogeneity among others. It anticipated that comprehensive will significantly contribute advancement research.
Language: Английский
Citations
33
Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)
Published: Oct. 11, 2024
The cascade of metastasis in tumor cells, exhibiting organ-specific tendencies, may occur at numerous phases the disease and progress under intense evolutionary pressures. Organ-specific relies on formation pre-metastatic niche (PMN), with diverse cell types complex interactions contributing to this concept, adding a new dimension traditional cascade. Prior metastatic dissemination, as orchestrators PMN formation, primary tumor-derived extracellular vesicles prepare fertile microenvironment for settlement colonization circulating cells distant secondary sites, significantly impacting cancer progression outcomes. Obviously, solely intervening sites passively after macrometastasis is often insufficient. Early prediction holistic, macro-level control represent future directions therapy. This review emphasizes dynamic intricate systematic alterations that progresses, illustrates immunological landscape creation, deepens understanding treatment modalities pertinent metastasis, thereby identifying some prognostic predictive biomarkers favorable early predict occurrence design appropriate combinations.
Language: Английский
Citations
21
Trends in Immunology, Journal Year: 2023, Volume and Issue: 44(11), P. 890 - 901
Published: Oct. 10, 2023
The therapeutic potential of interleukin (IL)-2 in cancer treatment has been known for decades, yet its widespread adoption clinical practice remains limited. Recently, chimeric proteins an anti-PD-1 antibody and suboptimal IL-2 variants were shown to stimulate potent antitumor antiviral immunity by inducing unique effector CD8
Language: Английский
Citations
27
Med, Journal Year: 2024, Volume and Issue: 5(3), P. 254 - 270.e8
Published: Feb. 28, 2024
Language: Английский
Citations
10
Journal for ImmunoTherapy of Cancer, Journal Year: 2025, Volume and Issue: 13(1), P. e009832 - e009832
Published: Jan. 1, 2025
Background More efficient therapeutic options for non-small cell lung cancer (NSCLC) are needed as the survival at 5 years of metastatic disease is near zero. In this regard, we used a preclinical model adenocarcinoma (SV2-OVA) to assess safety and efficacy novel radio-immunotherapy combining hypofractionated radiotherapy (HRT) with muPD1-IL2v immunocytokine muFAP-CD40 bispecific antibody. Methods We evaluated changes in immune microenvironment multiple timepoints following combination therapies investigated their underlying antitumor mechanisms. Additionally, analyzed tumor clonal heterogeneity upon treatments explore potential mechanisms associated lack complete response. Results The HRT had potent effect increased SV2-OVA model. Importantly, therapy was devoid measurable toxicity. It induced remodeling contexture through increase CD8 + T natural killer (NK) cells. addition treatment further infiltrating cells, expressing high levels effector molecules, both periphery core regions. An accumulation PD-1 TOX (exhausted) already ‘early’ timepoint, consistent limited clinical benefits provided by various study dynamics cells during progression highlighted selection HRT+muPD1-IL2v therapy. Conclusions demonstrated that strategy delay growth model, but additional studies required completely understand resistance response
Language: Английский
Citations
1
Cancers, Journal Year: 2024, Volume and Issue: 16(8), P. 1470 - 1470
Published: April 11, 2024
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with very poor prognosis. Despite advancements in treatment strategies, PDAC remains recalcitrant to therapies because patients are often diagnosed at an advanced stage. The stage of characterized by metastasis, which typically renders it unresectable surgery or untreatable chemotherapy. tumor microenvironment (TME) comprises proliferative myofibroblast-like cells and hosts the intense deposition extracellular matrix component that forms dense fibrous connective tissue, process called desmoplastic reaction. In TMEs, incessant aberration signaling pathways contributes immunosuppression suppressing antitumor immunity. This feature offers protective barrier impedes targeted delivery drugs. addition, efficacy immunotherapy compromised immune cold TME PDAC. Targeted therapy approaches towards stromal immunosuppressive TMEs challenging. this review, we discuss cellular non-cellular components contain actionable targets for drug development. We also highlight findings from preclinical studies provide updates about efficacies new investigational drugs clinical trials.
Language: Английский
Citations
5
Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)
Published: May 8, 2024
Abstract Despite advances in treatment strategies, colorectal cancer (CRC) continues to cause significant morbidity and mortality, with mounting evidence a close link between immune system dysfunctions issued. Interleukin-2 receptor gamma (IL-2RG) plays pivotal role as common subunit the IL-2 family cytokines activates JAK-STAT pathway. This study delves into of within tumor microenvironment investigates potential microRNAs (miRNAs) that directly inhibit IL-2RG, aiming discern their impact on CRC clinical outcomes. Bioinformatics analysis revealed upregulation IL-2RG mRNA TCGA-COAD samples showed strong correlations infiltration various lymphocytes. Single-cell corroborated these findings, highlighting expression critical cell subsets. To explore miRNA involvement dysregulation, was isolated from tissues lymphocytes 258 patients 30 healthy controls, cloned pcDNA3.1/CT-GFP-TOPO vector. Human embryonic kidney lines (HEK-293T) were transfected this construct. Our research involved comprehensive miRPathDB, miRWalk, Targetscan databases identify miRNAs associated 3′ UTR human IL-2RG. The microRNA (miRNA) molecules, hsa-miR-7-5p hsa-miR-26b-5p, have been identified potent suppressors patients. Specifically, downregulation hsa-miR-26b-5p has shown result Prognostic evaluation hsa-miR-7-5p, using data patient samples, established higher lower both poorer Additionally, several long non-coding RNAs (LncRNAs), such ZFAS1, SOX21-AS1, SNHG11, SNHG16, SNHG1, DLX6-AS1, GAS5, SNHG6, MALAT1, which may act competing endogenous RNA molecules for IL2RG by sequestering shared hsa-miR-26b-5p. In summary, investigation underscores utility serum tissue biomarkers predicting prognosis while also offering promise targets immunotherapy management. Graphical
Language: Английский
Citations
5
Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)
Published: Jan. 7, 2025
Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and deadly type cancer, with an extremely low five-year overall survival rate. To date, current treatment options primarily involve various chemotherapies, which often prove ineffective are associated substantial toxicity. Furthermore, immunotherapies utilizing checkpoint inhibitors have shown limited efficacy in this context, highlighting urgent need for novel therapeutic strategies. This study investigates preclinical innovative targeted therapy based on antibody-cytokine fusion proteins, specifically interleukin-2 (IL-2), a pivotal driver cell-mediated immunity, fused to L19 antibody, selectively binds extra domain B fibronectin (EDB-FN1) expressed tumor microenvironment. Methods We tested effectiveness different immunocytokines through vivo characterization syngeneic C57BL/6J orthotopic mouse models PDAC. Based these results, we decided focus L19-IL2. assess immunocytokine developed ex-vivo immune-spheroid interaction platform derived from murine 3D pancreatic cultures, telomerase reverse transcriptase (TERT) specific T-lymphocytes. Moreover, evaluated anti-cancer effect L19-IL2 combination standard experiments PDAC models. Tumor samples collected after treatments were characterized infiltrating immune cell components by bulk RNA sequencing (RNA-seq) spatial transcriptomics (Stereo-seq) analysis. Results The tumor-targeted protein demonstrated potent, dose-dependent anti-tumor activity mice tumors resistant chemotherapy. Spatial Transcriptomics (ST) RNA-seq analyses indicated that induced significant influx cells into microenvironment, expressing activation markers like granzymes, perforins, IL-2 receptors. Conclusions Our results enhances infiltration cytotoxicity, remodeling “cold” microenvironment (TME) improves outcomes, paving way strategies
Language: Английский
Citations
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