Current Opinion in Genetics & Development, Год журнала: 2024, Номер 90, С. 102300 - 102300
Опубликована: Дек. 24, 2024
Язык: Английский
Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)
Опубликована: Фев. 20, 2025
The progression of malignant tumors leads to the development secondary in various organs, including bones, brain, liver, and lungs. This metastatic process severely impacts prognosis patients, significantly affecting their quality life survival rates. Research efforts have consistently focused on intricate mechanisms underlying this corresponding clinical management strategies. Consequently, a comprehensive understanding biological foundations tumor metastasis, identification pivotal signaling pathways, systematic evaluation existing emerging therapeutic strategies are paramount enhancing overall diagnostic treatment capabilities for tumors. However, current research is primarily metastasis within specific cancer types, leaving significant gaps our complex cascade, organ-specific tropism mechanisms, targeted treatments. In study, we examine sequential processes elucidate driving organ-tropic systematically analyze tumors, those tailored organ involvement. Subsequently, synthesize most recent advances technologies challenges opportunities encountered pertaining bone metastasis. Our objective offer insights that can inform future practice crucial field.
Язык: Английский
Процитировано
7
Gut, Год журнала: 2025, Номер unknown, С. gutjnl - 333492
Опубликована: Янв. 9, 2025
Background The immune suppression mechanisms in pancreatic ductal adenocarcinoma (PDAC) remain unknown, but preclinical studies have implicated macrophage-mediated tolerance. Hence, pathways that regulate macrophage phenotype are of strategic interest, with reprogramming strategies focusing on inhibitors phosphoinositide 3-kinase-gamma (PI3Kγ) due to restricted cell expression. Inhibition PI3Kγ alone is ineffective PDAC, despite increased infiltration CD8+ T cells. Objective We hypothesised the stimulatory effects radiation, and its ability boost tumour antigen availability could synergise inhibition augment antitumour immunity. Design used orthoptic genetically engineered mouse models cancer (LSL-Kras G12D/+ ;Trp53 R172H/+ ;Pdx1-Cre). Stereotactic radiotherapy was delivered using contrast CT imaging, by oral administration. Changes microenvironment were quantified flow cytometry, multiplex immunohistochemistry RNA sequencing. Tumour-educated macrophages investigate efferocytosis, presentation activation. Single-cell sequencing data fresh samples autologous validate our findings. Results Tumour-associated employ efferocytosis eradicate apoptotic cells can be redirected present antigens, stimulate responses increase local control. Specifically, we demonstrate how signalling restricts inflammatory supports MERTK-dependent efferocytosis. further find combination targeted stimulates invoke a pathogen-induced like switches from tolerant presenting. Conclusions Our new immunotherapeutic approach translational rationale improve survival PDAC.
Язык: Английский
Процитировано
2
Small, Год журнала: 2025, Номер unknown
Опубликована: Янв. 10, 2025
Abstract Glioblastoma (GBM), the most malignant brain tumor with high prevalence, remains highly resistant to existing immunotherapies due significant immunosuppression within microenvironment (TME), predominantly manipulated by M2‐phenotypic tumor‐associated macrophages (M2‐TAMs). Here in this work, an M2‐TAMs targeted nano‐reprogrammers, MG5‐S‐IMDQ, is established decorating mannose molecule as targeting moiety well toll‐like receptor (TLR) 7/8 agonist, imidazoquinoline (IMDQ) on dendrimeric nanoscaffold. MG5‐S‐IMDQ demonstrated excellent capacity of penetrating blood‐brain barrier (BBB) selectively GBM microenvironment, leading a phenotype transformation and function restoration TAMs shown heightened phagocytic activity toward cells, enhanced cytotoxic effects, improved antigen cross‐presentation capability. In meantime, induction function‐oriented “gear effect”, treatment extended its impact systemically enhancing infiltration type I conventional dendritic cells (cDC1s) into sites bolstering adaptive immune responses. sum, precisely working unique target situ, nano‐reprogrammers successfully robust network that worked synergistically combat tumors. This facile nanoplatform‐based immunomodulatory strategy, serving powerful convenient monotherapy or complementary alongside other therapies like surgery, provided deep insights for advancing translational study GBM.
Язык: Английский
Процитировано
2
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2025, Номер 1880(2), С. 189281 - 189281
Опубликована: Фев. 8, 2025
Язык: Английский
Процитировано
2
Advanced Materials, Год журнала: 2025, Номер unknown
Опубликована: Фев. 16, 2025
The radiotherapy-induced release of DNA fragments can stimulate the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator interferon genes (cGAS-STING) pathway to prime antitumor immunity, but this is expected be less potent because inefficient cytosolic delivery negatively charged fragments. In study, manganese-coordinated chitosan (CS-Mn) microparticles with selective DNA-capturing capacity are concisely prepared via a coordination-directed one-pot synthesis process potentiate immunogenicity radiotherapy. obtained CS-Mn that undergo rapid disassembly under physiological conditions selectively bind form positively DNA-CS assemblies strong electrostatic interaction between linear and molecules. They thus enable efficient in presence serum cooperate Mn2+ activate cGAS-STING dendritic cells. Upon intratumoral injection, markedly enhance efficacy radiotherapy against both irradiated distal tumors different tumor models collectively promoting tumor-infiltrating CD8+ T-cell stemness activation innate immunity. radiosensitization effect further augmented by concurrently applying anti-programmed cell death protein 1 (anti-PD-1) immunotherapy. This work highlights an ingenious strategy prepare Trojan horse-like as cGAS-STING-activating radiosensitizers for effective radioimmunotherapy.
Язык: Английский
Процитировано
2
Cell, Год журнала: 2024, Номер unknown
Опубликована: Ноя. 1, 2024
Язык: Английский
Процитировано
9
Journal of Gastrointestinal Cancer, Год журнала: 2025, Номер 56(1)
Опубликована: Фев. 12, 2025
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers, with a 5-year survival rate that has improved only marginally over past 30 years, despite numerous clinical trials. PDAC poses several unique challenges, including early metastatic spread and predilection for liver metastasis. It is also highly resistant to anti-tumor immunity immunotherapy due its dense immunosuppressive tumor microenvironment, low immunogenicity, systemic immune suppression. mutational burden, defective antigen presentation, checkpoint molecule upregulation, which reduce recognition. Together, these factors leave as an "immune cold" minimal cytotoxic T-cell activity. Novel therapeutic approaches are urgently needed reinvigorate immunity. Recent advances, such adjuvant personalized mRNA neoantigen vaccines mutant-KRAS targeted vaccines, have demonstrated sustained vaccine-induced T cell responses associated recurrence-free in surgically resected PDAC. Combining different vaccine optimal sequencing chemotherapy, surgery, radiotherapy, other immunotherapies may further enhance outcomes. represent promising strategy overcoming PDAC's resistance conventional therapies, ongoing trials exploring their potential improve long-term survival.
Язык: Английский
Процитировано
1
Biology Direct, Год журнала: 2023, Номер 18(1)
Опубликована: Ноя. 1, 2023
Cancer immunotherapy, alone or in combination with conventional therapies, has revolutionized the landscape of antineoplastic treatments, dendritic cells (DC) emerging as key orchestrators anti-tumor immune responses. Among distinct DC subsets, type 1 (cDC1) have gained prominence due to their unique ability cross-present antigens and activate cytotoxic T lymphocytes. This review summarizes distinctive characteristics cDC1, pivotal role anticancer immunity, potential applications cDC1-based strategies immunotherapy.
Язык: Английский
Процитировано
11
Journal of Controlled Release, Год журнала: 2025, Номер 379, С. 537 - 548
Опубликована: Янв. 24, 2025
Язык: Английский
Процитировано
0
MedComm, Год журнала: 2025, Номер 6(1)
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
0