Insights into IL-6/JAK/STAT3 Signaling in the Tumor Microenvironment: Implications for Cancer Therapy

Cytokine & Growth Factor Reviews, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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The next frontier in immunotherapy: potential and challenges of CAR-macrophages

Experimental Hematology and Oncology, Год журнала: 2024, Номер 13(1)

Опубликована: Авг. 5, 2024

Abstract Chimeric antigen receptor macrophage (CAR-MΦ) represents a significant advancement in immunotherapy, especially for treating solid tumors where traditional CAR-T therapies face limitations. CAR-MΦ offers promising approach to target and eradicate tumor cells by utilizing macrophages’ phagocytic antigen-presenting abilities. However, challenges such as the complex microenvironment (TME), variability expression, immune suppression limit their efficacy. This review addresses these issues, exploring mechanisms of action, optimal construct designs, interactions within TME. It also delves into ex vivo manufacturing CAR-MΦ, discussing autologous allogeneic sources importance stringent quality control. The potential synergies integrating with existing cancer like checkpoint inhibitors conventional chemotherapeutics are examined highlight possible enhanced treatment outcomes. Furthermore, regulatory pathways scrutinized alongside established protocols cells, identifying unique considerations essential clinical trials market approval. Proposed safety monitoring frameworks aim manage adverse events, cytokine release syndrome, crucial patient safety. Consolidating current research insights, this seeks refine therapeutic applications, overcome barriers, suggest future directions transition from experimental platforms standard care options.

Язык: Английский

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Promising Therapeutic Strategies for Hematologic Malignancies: Innovations and Potential

Molecules, Год журнала: 2024, Номер 29(17), С. 4280 - 4280

Опубликована: Сен. 9, 2024

In this review we explore innovative approaches in the treatment of hematologic cancers by combining various therapeutic modalities. We discuss synergistic potential inhibitors targeting different cellular pathways with immunotherapies, molecular therapies, and hormonal therapies. Examples include PI3K proteasome inhibitors, NF-κB immunotherapy checkpoint neddylation therapies tumor microenvironment. Additionally, use small molecules peptide cancer treatment. These multidimensional combinations present promising strategies for enhancing efficacy overcoming resistance mechanisms. However, further clinical research is required to validate their effectiveness safety profiles patients.

Язык: Английский

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Decoding the Intricate Landscape of Pancreatic Cancer: Insights into Tumor Biology, Microenvironment, and Therapeutic Interventions

Cancers, Год журнала: 2024, Номер 16(13), С. 2438 - 2438

Опубликована: Июль 2, 2024

Pancreatic ductal adenocarcinoma (PDAC) presents significant oncological challenges due to its aggressive nature and poor prognosis. The tumor microenvironment (TME) plays a critical role in progression treatment resistance. Non-neoplastic cells, such as cancer-associated fibroblasts (CAFs) tumor-associated macrophages (TAMs), contribute growth, angiogenesis, immune evasion. Although cells infiltrate TME, evade responses by secreting chemokines expressing checkpoint inhibitors (ICIs). Vascular components, like endothelial pericytes, stimulate angiogenesis support while adipocytes secrete factors that promote cell invasion, Additionally, perineural characteristic feature of PDAC, contributes local recurrence Moreover, key signaling pathways including Kirsten rat sarcoma viral oncogene (KRAS), transforming growth factor beta (TGF-β), Notch, hypoxia-inducible (HIF), Wnt/β-catenin drive Targeting the TME is crucial for developing effective therapies, strategies inhibiting CAFs, modulating response, disrupting blocking neural interactions. A recent multi-omic approach has identified signature genes associated with anoikis resistance, which could serve prognostic biomarkers targets personalized therapy.

Язык: Английский

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Single-cell transcriptomics unveils multifaceted immune heterogeneity in early-onset versus late-onset cervical cancer

World Journal of Surgical Oncology, Год журнала: 2025, Номер 23(1)

Опубликована: Янв. 14, 2025

Early-onset (EOCC) and late-onset cervical cancers (LOCC) represent two clinically distinct subtypes, each defined by unique clinical manifestations therapeutic responses. However, their immunological profiles remain poorly explored. Herein, we analyzed single-cell transcriptomic data from 4 EOCC LOCC samples to compare immune architectures. Epithelial cells in exhibited a notable dual phenotype, characterized immune-suppressive properties driven elevated CXCL production, alongside immune-stimulatory features linked heightened HLA molecule expression. CD4 + CD8 T demonstrated activation state, while NK diminished cytotoxicity. Macrophages displayed enhanced polarization towards both M1 M2 phenotypes, along with dendritic showing augmented antigen-presenting capacity. Regarding cancer-associated fibroblasts (CAFs), was enriched inflammatory CAFs, whereas harbored higher proportion of CAFs. These findings reveal the multifaceted heterogeneity between LOCC, underscoring imperative for age-tailored immunotherapeutic strategies.

Язык: Английский

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Divergent Crosstalk Between Microglia and T Cells in Brain Cancers: Implications for Novel Therapeutic Strategies

Biomedicines, Год журнала: 2025, Номер 13(1), С. 216 - 216

Опубликована: Янв. 16, 2025

Background: Brain cancers represent a formidable oncological challenge characterized by their aggressive nature and resistance to conventional therapeutic interventions. The tumor microenvironment has emerged as critical determinant of progression treatment efficacy. Within this complex ecosystem, microglia macrophages play fundamental roles, forming intricate networks with peripheral immune cell populations, particularly T cells. precise mechanisms underlying microglial interactions cells contributions immunosuppression remain incompletely understood. Methods: This review comprehensively examines the cellular dialogue between in two prominent brain malignancies: primary glioblastoma secondary metastases. Results: Through comprehensive current scientific literature, we explore nuanced through which microglial-T modulate growth responses. Conclusions: Our analysis seeks unravel communication pathways that potentially underpin progression, ultimate goal illuminating novel strategies for cancer intervention.

Язык: Английский

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Based on the immune system: the role of the IL-2 family in pancreatic disease

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Янв. 31, 2025

The IL-2 family, consisting of IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21, is a key regulator the immune response. As an important endocrine digestive organ, function pancreas regulated by system. Studies have shown that each cytokine family influences occurrence development pancreatic diseases participating in regulation In this paper, we review structural functional characteristics members, focus on their molecular mechanisms including acute pancreatitis, chronic pancreatitis cancer, highlight importance related proteins response disease progression, which will provide valuable insights for new biomarkers diseases, early diagnosis assessment severity, therapeutic regimens. study are summarized following sections.

Язык: Английский

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Pan-cancer characterization of C–C motif chemokine ligand 5 (CCL5) identifies its role as biomarker and therapeutic target

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Март 4, 2025

C–C Motif Chemokine Ligand 5 (CCL5) is known for its role in immune regulation and has been implicated cancer progression. However, expression prognostic significance pan-cancer require comprehensive evaluation. This study was initiated to decipher the of CCL5 genes. In silico analyses involving various online databases molecular experiments knockdown KIRC cell lines evaluated proliferation, colony formation, migration. significantly up-regulated several cancers. High correlated with poorer overall survival kidney renal carcinoma (KIRC) esophageal (ESCA) patients. Promoter hypomethylation elevated prognosis. mutations were rare; indicating driven by overexpression rather than genetic alterations. Positive correlations inhibitory MHC genes suggested CCL5's fostering an immunosuppressive tumor microenvironment. increased infiltration, particularly CD8 T cells macrophages. did not influence drug sensitivity. resulted reduced migration, underscoring critical dynamics. Our highlights progression prognosis, ESCA. modulating microenvironment potential as a therapeutic target warrant further investigation.

Язык: Английский

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Introductory Chapter: New Updates in Tumor Microenvironment

IntechOpen eBooks, Год журнала: 2025, Номер unknown

Опубликована: Фев. 26, 2025

Язык: Английский

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Identification of methionine metabolism related prognostic model and tumor suppressive functions of BHMT in hepatocellular carcinoma

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Март 18, 2025

Given the resistance to conventional treatments and limitations of immune checkpoint blockade therapy in hepatocellular carcinoma (HCC), it is imperative explore novel prognostic models biomarkers. The dependence cancer cell on exogenous methionine, known as Hoffman effect, a hallmark HCC, with numerous studies reporting strong correlation between methionine metabolism tumor development. Betaine-homocysteine S-methyltransferase (BHMT), critical component pathway, has polymorphisms linking poor prognosis multiple cancers. Nevertheless, there little literature regarding relationship incidence, mortality well function BHMT HCC progression. In this study, by analyzing datasets, we constructed metabolism-related model thoroughly investigated influence HCC. Bioinformatics analysis revealed marked decrease expression which was linked adverse clinical outcomes. CIBERSORT results suggest that promotes infiltration M1 macrophages. Our its potential an ideal biomarker for anti PD-L1 immunotherapy. summary, study innovatively provides first unveils suppressive providing mechanism exert function.

Язык: Английский

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