Rheumatic Immune-Related Adverse Events due to Immune Checkpoint Inhibitors—A 2023 Update DOI Open Access
Quang Minh Dang, Ryu Watanabe,

Mayu Shiomi

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5643 - 5643

Published: March 15, 2023

With the aging of population, malignancies are becoming common complications in patients with rheumatoid arthritis (RA), particularly elderly patients. Such often interfere RA treatment. Among several therapeutic agents, immune checkpoint inhibitors (ICIs) which antagonize immunological brakes on T lymphocytes have emerged as a promising treatment option for variety malignancies. In parallel, evidence has accumulated that ICIs associated numerous immune-related adverse events (irAEs), such hypophysitis, myocarditis, pneumonitis, and colitis. Moreover, not only exacerbate pre-existing autoimmune diseases, but also cause de novo rheumatic disease–like symptoms, arthritis, myositis, vasculitis, currently termed irAEs. Rheumatic irAEs differ from classical diseases multiple aspects, should be individualized based severity. Close collaboration oncologists is critical preventing irreversible organ damage. This review summarizes current regarding mechanisms management focus vasculitis. Based these findings, potential strategies against discussed.

Language: Английский

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

et al.

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(8), P. 2121 - 2132

Published: July 6, 2023

Language: Английский

Citations

221
Insights from a 30-year journey: function, regulation and therapeutic modulation of PD1 DOI
Kenji Chamoto, Tomonori Yaguchi, Masaki Tajima

et al.

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 23(10), P. 682 - 695

Published: April 25, 2023

Language: Английский

Citations

95
Role of mitochondrial alterations in human cancer progression and cancer immunity DOI Creative Commons
Sheng‐Fan Wang, Ling‐Ming Tseng, Hsin‐Chen Lee

et al.

Journal of Biomedical Science, Journal Year: 2023, Volume and Issue: 30(1)

Published: July 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.

Language: Английский

Citations

66
Senescence drives immunotherapy resistance by inducing an immunosuppressive tumor microenvironment DOI Creative Commons
Damien Maggiorani,

Oanh Lê,

Véronique Lisi

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 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.

Language: Английский

Citations

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

et al.

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(9), P. 1571 - 1584

Published: Aug. 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.

Language: Английский

Citations

37
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

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(1), P. 113661 - 113661

Published: Jan. 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.

Language: Английский

Citations

23
The aged tumor microenvironment limits T cell control of cancer DOI
Chang-Yu Chen,

Sneha Jaiswal,

Daniela Martínez

et al.

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(6), P. 1033 - 1045

Published: May 14, 2024

Language: Английский

Citations

23
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

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(22)

Published: April 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

Language: Английский

Citations

22
Aggregation-Induced Emission Luminogen: Role in Biopsy for Precision Medicine DOI Creative Commons
Yanhong Duo, Lei Han, Yaoqiang Yang

et al.

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(20), P. 11242 - 11347

Published: Oct. 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),

Language: Английский

Citations

19
Lactobacillus reuteri ZJ617 attenuates metabolic syndrome via microbiota-derived spermidine DOI Creative Commons
Yanfei Ma, Yifan Zhong, Wenjie Tang

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 21, 2025

Metabolic syndrome (MetS) is a difficult-to-manage disease that poses significant risk to human health. Here, we show the supplementation of Lactobacillus reuteri ZJ617 ameliorates symptoms MetS in mice induced by high-fat diet. L. modulates host metabolism interacting with microbiome, resulting production spermidine synthesized microbiota. serves as source substrates for microbiota synthesize spermidine, hence preventing decline bacteria responsible production. Spermidine treatment mimics metabolic effects ZJ617, whereas pharmacological inhibition biosynthesis abolishes these benefits. Our findings reveal mechanism which alleviates and provide support its potential use probiotic promoting Intestinal commensal are closely associated authors mitigates supplying substrate S-adenosylmethionine spermidine-producing promote synthesis intestine.

Language: Английский

Citations

2