International Immunopharmacology, Год журнала: 2025, Номер 154, С. 114505 - 114505
Опубликована: Март 31, 2025
Язык: Английский
Cell Death and Disease, Год журнала: 2024, Номер 15(2)
Опубликована: Фев. 1, 2024
Abstract Although immunotherapy has made breakthrough progress, its efficacy in solid tumours remains unsatisfactory. Exosomes are the main type of extracellular vesicles that can deliver various intracellular molecules to adjacent or distant cells and organs, mediating biological functions. Studies have found exosomes both activate immune system inhibit system. The antigen major histocompatibility complex (MHC) carried make it possible develop them as anticancer vaccines. derived from blood, urine, saliva cerebrospinal fluid be used ideal biomarkers cancer diagnosis prognosis. In recent years, exosome-based therapy great progress fields drug transportation immunotherapy. Here, we review composition sources microenvironment further elaborate on potential mechanisms pathways by which influence for cancers. Moreover, summarize clinical application prospects engineered exosome vaccines Eventually, these findings may open up avenues determining diagnosis, treatment, prognosis
Язык: Английский
Процитировано
42
Nature Communications, Год журнала: 2024, Номер 15(1)
Опубликована: Июль 18, 2024
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with dismal prognosis due to distant metastasis, even in the early stage. Using RNA sequencing and multiplex immunofluorescence, here we find elevated expression of mixed lineage kinase domain-like pseudo-kinase (MLKL) enhanced necroptosis pathway PDAC from liver metastasis T-stage (T1M1) patients comparing non-metastatic (T1M0) patients. Mechanistically, MLKL-driven recruits macrophages, enhances tumor CD47 ‘don’t eat me’ signal, induces macrophage extracellular traps (MET) formation for CXCL8 activation. further initiates epithelial–mesenchymal transition (EMT) upregulates ICAM-1 promote endothelial adhesion. METs also degrades matrix, that eventually supports metastasis. Meanwhile, targeting reduces vivo. Our study thus reveals facilitates by evading immune surveillance, suggest blockade, combined MLKL inhibitor GW806742X, may be promising neoadjuvant immunotherapy overcoming T1M1 dilemma reviving opportunity radical surgery.
Язык: Английский
Процитировано
17
British Journal of Pharmacology, Год журнала: 2025, Номер unknown
Опубликована: Янв. 7, 2025
Abstract Background and Purpose Tumour hypoxia frequently presents a major challenge in the treatment of neuroblastoma (NBL). The cells produce carbonic anhydrase IX (CA IX), an enzyme crucial for survival cancer low‐oxygen environments. Experimental Approach We designed synthesised novel high‐affinity inhibitor CA IX. highest to‐date. affinities were determined all human catalytically active isozymes showing significant selectivity over other isozymes. effect on cell growth was vitro vivo via mice xenograft model. Key Results effectively mitigated acidification induced by reduced spheroid under hypoxic conditions SK‐N‐AS line. It also diminished secretion pro‐tumour chemokines IL‐8 (CXCL2) CCL2. When we combined this with compound that inhibits chemokine receptor CCR2 protein activity, observed reduction mouse tumour growth. prompted tumours to exhibit adaptive resistance producing higher levels vascular endothelial factor receptors (VEGFR) compensatory signals. Conclusions Implications This research underscores pivotal role potential inhibitor‐based combination intervention therapy treatment.
Язык: Английский
Процитировано
2
Cells, Год журнала: 2024, Номер 13(10), С. 844 - 844
Опубликована: Май 16, 2024
Immune cell migration is required for the development of an effective and robust immune response. This elegant process regulated by both cellular environmental factors, with variables such as state, anatomical location, disease state that govern differences in patterns. In all cases, a major factor expression surface receptors their cognate ligands. Rapid adaptation to conditions partly depends on intrinsic factors affect cell’s ability adjust new environment. this review, we discuss myeloid lymphoid cells outline key determinants migration, including molecules adhesion, modes chemotaxis, specific chemokine signaling. Furthermore, summarize tumor-specific elements contribute trafficking cancer, while also exploring microenvironment can alter these dynamics within tumor pro antitumor fashion. Specifically, highlight importance secretome later aspects. review considers myriad impact trajectory cancer. We aim immunotherapeutic targets be harnessed achieve controlled tumors.
Язык: Английский
Процитировано
12
Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(20)
Опубликована: Май 7, 2024
The immune landscape of bladder cancer progression is not fully understood, and effective therapies are lacking in advanced cancer. Here, we visualized that cells recruited neutrophils by secreting interleukin-8 (IL-8); turn, played dual functions cancer, including hepatocyte growth factor (HGF) release CCL3 high PD-L1 super-immunosuppressive subset formation. Mechanistically, c-Fos was identified as the mediator HGF up-regulating IL-8 transcription cells, which central to positive feedback neutrophil recruitment. Clinically, compared with serum IL-8, urine a better biomarker for prognosis clinical benefit checkpoint blockade (ICB). Additionally, targeting or receptor (MET) signaling combined ICB inhibited boosted antitumor effect CD8 + T mice. These findings reveal mechanism tumor–neutrophil cross talk orchestrates microenvironment provide combination strategies, may have broad impacts on patients suffering from malignancies enriched neutrophils.
Язык: Английский
Процитировано
11
Science Advances, Год журнала: 2024, Номер 10(8)
Опубликована: Фев. 23, 2024
Glycolytic metabolism may account for antitumor immunity failure. Pyruvate kinase M2 (PKM2) and platelet phosphofructokinase (PFKP), two key enzymes involved in the glycolytic pathway, are hyperactivated head neck squamous cell carcinoma (HNSCC). Using ganetespib as a drug model heat shock protein 90 (HSP90) inhibition combining results from clinical trials animal treatment, we demonstrated that HSP90 leads to blockade of flux HNSCC cells by simultaneously suppressing PKM2 PFKP at both transcriptional posttranslational levels. Down-regulation tumor glycolysis facilitates infiltration cytotoxic T via suppression glycolysis-dependent interleukin-8 signaling. The addition radiation attenuates radiation-induced up-regulation potentiates cell–mediated immunity, resulting more potent effect than either treatment alone, providing molecular basis exploring combination inhibitors with radiotherapy improve outcomes patients HNSCC.
Язык: Английский
Процитировано
10
Frontiers in Immunology, Год журнала: 2025, Номер 16
Опубликована: Янв. 22, 2025
Glioblastoma (GBM) cells leverage complex endogenous and environmental regulatory mechanisms to drive proliferation, invasion, metastasis. Tumor immune evasion, facilitated by a multifactorial network, poses significant challenge effective therapy, as evidenced the limited clinical benefits of monotherapies, highlighting adaptive nature evasion. This review explores glioblastoma’s evasion mechanisms, role ICIs in tumor microenvironment, recent advancements, offering theoretical insights directions for monotherapy combination therapy glioblastoma management.
Язык: Английский
Процитировано
1
Frontiers in Immunology, Год журнала: 2025, Номер 16
Опубликована: Фев. 7, 2025
This paper explored the novel approach of targeting cyclic guanosine monophosphate (GMP)-adenosine (AMP) synthase-stimulator interferon genes (cGAS-STING) pathway for treatment osteosarcoma (OS). Osteosarcoma is a common malignancy in adolescents. Most patients die from lung metastasis. It reviewed epidemiology and pathological characteristics OS, highlighting its highly malignant nature tendency pulmonary metastasis, underscoring importance identifying new therapeutic targets. The cGAS-STING was closely associated with biological behaviors OS cells, suggesting that this could be promising strategy. Currently, research on role has been limited, underlying mechanisms remain unclear. Therefore, further investigation into exploration strategies based are great significance developing more effective treatments OS. offered fresh perspective providing hope options by pathway.
Язык: Английский
Процитировано
1
Gastric Cancer, Год журнала: 2023, Номер 26(5), С. 691 - 707
Опубликована: Июнь 10, 2023
Язык: Английский
Процитировано
21
Trends in cancer, Год журнала: 2024, Номер 10(7), С. 655 - 667
Опубликована: Апрель 24, 2024
Neutrophils, major regulators of innate immunity, have recently emerged as key components the tumor microenvironment. The role neutrophils in cancer has been linked to their ability form neutrophil extracellular traps (NETs), structures composed decondensed DNA decorated with enzymes that are released into space. Here, we discuss pivotal roles NETs influencing responses anticancer therapies such chemotherapy, radiotherapy, immunotherapy, and targeted therapy. Highlighting recent insights, delve dual nature context treatments, examining potential either counteract or enhance treatment outcomes. Strategic targeting may be a promising avenue for crafting combination resistance treatments' efficacy.
Язык: Английский
Процитировано
8