Magnetic Metal–Organic Framework-Based Nanoplatform with Platelet Membrane Coating as a Synergistic Programmed Cell Death Protein 1 Inhibitor against Hepatocellular Carcinoma DOI Creative Commons

Hong Guo,

Yuping Liu, Xia Li

и другие.

ACS Nano, Год журнала: 2023, Номер 17(23), С. 23829 - 23849

Опубликована: Ноя. 22, 2023

Programmed cell death protein 1 (PD-1) inhibitors are the most common immune-checkpoint and considered promising drugs for hepatocellular carcinoma (HCC). However, in clinical settings, they have a low objective response rate (15%–20%) patients with HCC; this is because of insufficient level activity tumor-infiltrating T lymphocytes (TILs). The combined administration oxymatrine (Om) astragaloside IV (As) can increase levels TILs by inhibiting activation cancer-associated fibroblasts (CAFs) improve enhancing their mitochondrial function. In present study, we constructed magnetic metal–organic framework (MOF)-based nanoplatform platelet membrane (Pm) coating (PmMN@Om&As) to simultaneously deliver Om As into HCC microenvironment. We observed that PmMN@Om&As exhibited high total drug-loading capacity (33.77 wt %) good immune escape. Furthermore, it target tissues field exert long-lasting effects. microenvironment accelerated disintegration release Om&As, thereby increasing regulating CAFs function TILs. addition, carrier could synergize Om&As oxygen consumption proton efflux TILs, upregulating Combination therapy α-PD-1 resulted tumor suppression 84.15% prolonged survival time mice. Our study provides approach improving antitumor effect immunotherapy HCC.

Язык: Английский

Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial DOI
Bertrand Routy, John Lenehan, Wilson H. Miller

и другие.

Nature Medicine, Год журнала: 2023, Номер 29(8), С. 2121 - 2132

Опубликована: Июль 6, 2023

Язык: Английский

Процитировано

234
Insights from a 30-year journey: function, regulation and therapeutic modulation of PD1 DOI
Kenji Chamoto, Tomonori Yaguchi, Masaki Tajima

и другие.

Nature reviews. Immunology, Год журнала: 2023, Номер 23(10), С. 682 - 695

Опубликована: Апрель 25, 2023

Язык: Английский

Процитировано

96
Role of mitochondrial alterations in human cancer progression and cancer immunity DOI Creative Commons
Sheng‐Fan Wang, Ling‐Ming Tseng, Hsin‐Chen Lee

и другие.

Journal of Biomedical Science, Год журнала: 2023, Номер 30(1)

Опубликована: Июль 31, 2023

Abstract Dysregulating cellular metabolism is one of the emerging cancer hallmarks. Mitochondria are essential organelles responsible for numerous physiologic processes, such as energy production, metabolism, apoptosis, and calcium redox homeostasis. Although “Warburg effect,” in which cells prefer aerobic glycolysis even under normal oxygen circumstances, was proposed a century ago, how mitochondrial dysfunction contributes to progression still unclear. This review discusses recent progress alterations DNA (mtDNA) dynamics malignant progression. Moreover, we integrate possible regulatory mechanism dysfunction–mediated retrograde signaling pathways, including mitochondrion-derived molecules (reactive species, calcium, oncometabolites, mtDNA) stress response pathways (mitochondrial unfolded protein integrated response) provide therapeutic targets. Furthermore, discuss findings on role mitochondria immune function reveal impact tumor microenvironment remodeling immunity. Targeting might improve immunotherapy. These suggest that targeting malignancy modulating immunity be promising treatment strategies patients precise personalized medicine against cancer.

Язык: Английский

Процитировано

69
Senescence drives immunotherapy resistance by inducing an immunosuppressive tumor microenvironment DOI Creative Commons
Damien Maggiorani,

Oanh Lê,

Véronique Lisi

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 18, 2024

The potential of immune checkpoint inhibitors (ICI) may be limited in situations where cell fitness is impaired. Here, we show that the efficacy cancer immunotherapies compromised by accumulation senescent cells mice and context therapy-induced senescence (TIS). Resistance to immunotherapy associated with a decrease activation CD8 T within tumors. Elimination restores homeostasis tumor micro-environment (TME) increases survival response immunotherapy. Using single-cell transcriptomic analysis, observe injection ABT263 (Navitoclax) reverses exacerbated immunosuppressive profile myeloid TME. these also proliferation vitro abrogates resistance vivo. Overall, our study suggests use senolytic drugs before ICI constitute pharmacological approach improve effectiveness immunotherapies.

Язык: Английский

Процитировано

38
Spermidine is essential for fasting-mediated autophagy and longevity DOI Creative Commons
Sebastian J. Hofer, Ioanna Daskalaki, Martina Bergmann

и другие.

Nature Cell Biology, Год журнала: 2024, Номер 26(9), С. 1571 - 1584

Опубликована: Авг. 8, 2024

Abstract Caloric restriction and intermittent fasting prolong the lifespan healthspan of model organisms improve human health. The natural polyamine spermidine has been similarly linked to autophagy enhancement, geroprotection reduced incidence cardiovascular neurodegenerative diseases across species borders. Here, we asked whether cellular physiological consequences caloric depend on metabolism. We report that levels increased upon distinct regimens or in yeast, flies, mice volunteers. Genetic pharmacological blockade endogenous synthesis fasting-induced nematodes cells. Furthermore, perturbing pathway vivo abrogated lifespan- healthspan-extending effects, as well cardioprotective anti-arthritic fasting. Mechanistically, mediated these effects via induction hypusination translation regulator eIF5A. In summary, polyamine–hypusination axis emerges a phylogenetically conserved metabolic control hub for fasting-mediated enhancement longevity.

Язык: Английский

Процитировано

38
Spermidine‐Functionalized Injectable Hydrogel Reduces Inflammation and Enhances Healing of Acute and Diabetic Wounds In Situ DOI Creative Commons
Qianqian Wu,

Runjiao Yang,

Wenxuan Fan

и другие.

Advanced Science, Год журнала: 2024, Номер 11(22)

Опубликована: Апрель 11, 2024

Abstract The inflammatory response is a key factor affecting tissue regeneration. Inspired by the immunomodulatory role of spermidine, an injectable double network hydrogel functionalized with spermidine (DN‐SPD) developed, where first and second networks are formed dynamic imine bonds non‐dynamic photo‐crosslinked respectively. single before photo‐crosslinking exhibits excellent injectability thus can be printed in situ to form hydrogels. DN‐SPD has demonstrated desirable mechanical properties adhesion. More importantly, “operando” comparison hydrogels loaded or diethylenetriamine (DETA), sham molecule resembling shown similar physical properties, but quite different biological functions. Specifically, outcomes 3 sets vivo animal experiments demonstrate that not only reduce inflammation caused implanted exogenous biomaterials reactive oxygen species also promote polarization macrophages toward regenerative M2 phenotype, DN‐DETA hydrogel. Moreover, immunoregulation translate into faster more natural healing both acute wounds diabetic wounds. Hence, local administration affords simple elegant approach attenuate foreign body reactions induced treat chronic refractory

Язык: Английский

Процитировано

26
VISTA promotes the metabolism and differentiation of myeloid-derived suppressor cells by STAT3 and polyamine-dependent mechanisms DOI Creative Commons
Keman Zhang, Amin Zakeri, Tyler J. Alban

и другие.

Cell Reports, Год журнала: 2024, Номер 43(1), С. 113661 - 113661

Опубликована: Янв. 1, 2024

Myeloid-derived suppressor cells (MDSCs) impair antitumor immune responses. Identifying regulatory circuits during MDSC development may bring new opportunities for therapeutic interventions. We report that the V-domain of T cell activation (VISTA) functions as a key enabler differentiation. VISTA deficiency reduced STAT3 and STAT3-dependent production polyamines, which causally impaired mitochondrial respiration expansion. In both mixed bone marrow (BM) chimera mice myeloid-specific conditional knockout mice, significantly tumor-associated MDSCs but expanded monocyte-derived dendritic (DCs) enhanced cell-mediated tumor control. Correlated expression arginase-1 (ARG1), enzyme supporting polyamine biosynthesis, was observed in multiple human cancer types. endometrial cancer, co-expression ARG1 on myeloid is associated with poor survival. Taken together, these findings unveil VISTA/polyamine axis central regulator differentiation warrant therapeutically targeting this immunotherapy.

Язык: Английский

Процитировано

25
The aged tumor microenvironment limits T cell control of cancer DOI
Chang-Yu Chen,

Sneha Jaiswal,

Daniela Martínez

и другие.

Nature Immunology, Год журнала: 2024, Номер 25(6), С. 1033 - 1045

Опубликована: Май 14, 2024

Язык: Английский

Процитировано

25
Aggregation-Induced Emission Luminogen: Role in Biopsy for Precision Medicine DOI Creative Commons
Yanhong Duo, Lei Han, Yaoqiang Yang

и другие.

Chemical Reviews, Год журнала: 2024, Номер 124(20), С. 11242 - 11347

Опубликована: Окт. 9, 2024

Biopsy, including tissue and liquid biopsy, offers comprehensive real-time physiological pathological information for disease detection, diagnosis, monitoring. Fluorescent probes are frequently selected to obtain adequate on processes in a rapid minimally invasive manner based their advantages biopsy. However, conventional fluorescent have been found show aggregation-caused quenching (ACQ) properties, impeding greater progresses this area. Since the discovery of aggregation-induced emission luminogen (AIEgen) promoted advancements molecular bionanomaterials owing unique high quantum yield (QY) signal-to-noise ratio (SNR),

Язык: Английский

Процитировано

22
The role of polyamine metabolism in cellular function and physiology DOI
Ryan Schibalski,

Anastasia S. Shulha,

Betty P. Tsao

и другие.

AJP Cell Physiology, Год журнала: 2024, Номер 327(2), С. C341 - C356

Опубликована: Июнь 17, 2024

Polyamines are molecules with multiple amino groups that essential for cellular function. The major polyamines putrescine, spermidine, spermine, and cadaverine. important posttranscriptional regulation, autophagy, programmed cell death, proliferation, redox homeostasis, ion channel Their levels tightly controlled. High of associated proliferative pathologies such as cancer, whereas low polyamine observed in aging, elevated turnover enhances oxidative stress. Polyamine metabolism is implicated several pathophysiological processes the nervous, immune, cardiovascular systems. Currently, manipulating under investigation a potential preventive treatment pathologies, including ischemia/reperfusion injury, pulmonary hypertension, cancer. Although have been many intracellular mechanisms, our understanding these remains incomplete topic ongoing investigation. Here, we discuss regulation functions polyamines, their role physiology pathology, emphasize current gaps knowledge future research directions.

Язык: Английский

Процитировано

18