Adjuvant dendritic cell-based immunotherapy in melanoma: insights into immune cell dynamics and clinical evidence from a phase II trial DOI Creative Commons
Jenny Bulgarelli, Claudia Piccinini, Emanuela Scarpi

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 18, 2025

Abstract Background Dendritic cells (DCs) are the most efficient antigen-presenting and play a central role in immune system, orchestrating response against tumors. We previously demonstrated that DC-based vaccination effectively induces anti-tumor immunity, yet at same time showing robust safety profile, making this treatment potential candidate for effective adjuvant immunotherapy. To explore possibility, we designed randomized phase II trial (EudraCT no. 2014-005123-27) to provide complementary autologous DC patients (pts) with resected stage III/IV melanoma. Methods Overall, total of 18 eligible pts were included study, 10 whom received 6 monthly cycles combined IL-2 administration (arm A), 8 enrolled follow-up observational cohort B). A deep biomarkers profiling by multiplex immunoassay, human leukocyte antigens (HLA) typing, multiparametric flow cytometry situ tumor microenvironment analysis was performed entire cohort. The immunological assessed vivo DTH test ex selected melanoma-associated applying IFN-γ ELISPOT assay. Results Pts receiving showed better relapse-free survival compared (median 6.6 months, 95% CI, 2.3–not reached (nr) A) vs 5.2 2.5–nr B), not significant), favorable trends female 15.5 2.6–nr (female) 3.3, 2.3–nr (male)), less than 60 years 22.5 (age < 60) 4.7 ≥ 60), wild-type BRAF status 8.6–nr (BRAF wt) 3.8 mutated). toxicity profile favourable, no severe adverse events only mild, manageable reactions. Moreover, additional data suggested increased modulation vaccinated patients, which may reflect shift dynamics. Conclusions Our findings support tolerability as an melanoma, demonstrating significant both site peripherally relapsed non-relapsed patients. These results highlight autologous, personalised therapies pave way development innovative immunotherapy combinations future strategies. Trial registration ClinicalTrials.gov NCT02718391; EudraCT 2014-005123-27.

Language: Английский

The balance of STING signaling orchestrates immunity in cancer DOI

Klara Rasmussen Bollerup Lanng,

Emil Leth Lauridsen,

Martin R. Jakobsen

et al.

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(7), P. 1144 - 1157

Published: June 25, 2024

Language: Английский

Citations

45
cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment DOI Creative Commons
Hongying Zhang, Yongliang Liu,

Jieya Liu

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: Jan. 17, 2024

Cancer is a complex disease resulting from abnormal cell growth that induced by number of genetic and environmental factors. The tumor microenvironment (TME), which involves extracellular matrix, cancer-associated fibroblasts (CAF), tumor-infiltrating immune cells angiogenesis, plays critical role in progression. Cyclic adenosine monophosphate (cAMP) second messenger has pleiotropic effects on the TME. downstream effectors cAMP include cAMP-dependent protein kinase (PKA), exchange activated (EPAC) ion channels. While can activate PKA or EPAC promote cancer growth, it also inhibit proliferation survival context- type-dependent manner. Tumor-associated stromal cells, such as CAF release cytokines factors either stimulate production within Recent studies have shown targeting signaling TME therapeutic benefits cancer. Small-molecule agents adenylate cyclase been to growth. In addition, cAMP-elevating agents, forskolin, not only induce death, but directly some types. this review, we summarize current understanding biology immunology discuss basis for its context-dependent dual oncogenesis. Understanding precise mechanisms interact will be development effective therapies. Future aimed at investigating cAMP-cancer axis regulation may provide new insights into underlying tumorigenesis lead novel strategies.

Language: Английский

Citations

37
The impact of interleukin-6 (IL-6) and mesenchymal stem cell-derived IL-6 on neurological conditions DOI Creative Commons
Irina Kerkis, Álvaro Rossan de Brandão Prieto da Silva, Rodrigo Pinheiro Araldi

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: June 24, 2024

Interleukin-6 (IL-6) is a versatile cytokine crucial for immune response modulation, inflammation regulation, and various physiological processes in the body. Its wide-ranging functions underscore its importance maintaining health. Dysregulated IL-6 closely associated with many diseases, making it key research therapeutic target. Elevated levels central nervous system worsen neuroinflammation neurodegenerative diseases by activating microglia astrocytes releasing pro-inflammatory cytokines neurotoxic molecules. Moreover, dysregulated weakens blood-brain barrier, exacerbating neuronal damage allowing peripheral cells inflammatory mediators to enter brain. Mesenchymal stem (MSCs) show promise modulating regulating levels. They effectively suppress cytokines, including IL-6, while promoting anti-inflammatory factors. This approach highlights of targeting other alleviate adverse effects on neurological disorders. review provides comprehensive overview IL-6’s involvement disorders, examining endogenous derived from MSCs. We explore mechanisms affecting function, survival, modulation system. Additionally, we discuss potential MSC-derived neuroregeneration neuroprotection. By elucidating interplay pathologies, this offers insights into novel strategies signaling pathways

Language: Английский

Citations

14
Physical activity and exercise health benefits: cancer prevention, interception, and survival DOI
Adriana Albini, Carlo La Vecchia, Francesca Magnoni

et al.

European Journal of Cancer Prevention, Journal Year: 2024, Volume and Issue: 34(1), P. 24 - 39

Published: May 29, 2024

Physical activity (PA) has an established role in the promotion of health and fitness prevention disease. Expected overall benefits include reduction all-cause morbidity death, weight control, improved quality life, bone decreased falls elderly subjects, , deeper cognition, reduced risk depression, anxiety, sleeplessness. Currently, PA is a mainstay management cardiovascular diseases, metabolic syndrome, diabetes, health. Recently, perception its primary secondary prevention, interception, treatment cancer, however, also gaining importance. Regular walking, simplest type PA, associated with disease mortality, cancer increasing interest. Furthermore, improves life patients, attenuating side effects chemotherapy, decreasing sarcopenia, fitness, inhibiting recurrence progression some types. It promotes emotional psychological inducing positive changes. While mechanisms, effective levels useful amount practice are well cardiology, they yet to be fully determined oncology. Nevertheless, recommended reduce general population, it been introduced programs for second cancers. In perspective, will help as integrative therapy patients survivors. The number beneficial continuum highlighted this review.

Language: Английский

Citations

10
Grooved Microneedle Patch Augments Adoptive T Cell Therapy Against Solid Tumors via Diverting Regulatory T Cells DOI
Ruyi Zhou, Hao Yu, Tao Sheng

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(30)

Published: June 6, 2024

Abstract The efficacy of adoptive T cell therapy (ACT) for the treatment solid tumors remains challenging. In addition to poor infiltration effector (Teff) cells limited by physical barrier surrounding tumor, another major obstacle is extensive regulatory (Treg) cells, a immunosuppressive immune subset, in tumor microenvironment. Here, this work develops grooved microneedle patch augmenting ACT, aiming simultaneously overcome and barriers. microneedles are engineered through an ice‐templated method generate structure sufficient T‐cell loading. addition, with surface modification chemokine CCL22, MNs could not only directly deliver tumor‐specific into penetration, but also specifically divert Treg from microenvironment via cytokine concentration gradient, leading increase ratio Teff cells/Treg mouse melanoma model. Consequently, local delivery strategy both receptor chimeric antigen CCL22‐modified as niche significantly enhance antitumor reduce on‐target off‐tumor toxicity ACT.

Language: Английский

Citations

9
Unveiling the role of interleukin-6 in pancreatic cancer occurrence and progression DOI Creative Commons

Meihui Song,

Ying Tang,

Kaimei Cao

et al.

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: May 17, 2024

Pancreatic cancer is difficult to diagnose early and progresses rapidly. Researchers have found that a cytokine called Interleukin-6 (IL-6) involved in the entire course of pancreatic cancer, promoting its occurrence development. From earliest stages intraepithelial neoplasia invasion metastasis cells appearance tumor cachexia, IL-6 drives oncogenic signal transduction pathways immune escape accelerate disease progression. considered biomarker for diagnosis prognosis, as well potential target treatment. antibodies are currently being explored hot topic oncology. This article aims systematically explain how induces deterioration normal cells, with goal finding breakthrough

Language: Английский

Citations

8
Gold Nanoparticles Downregulate IL-6 Expression/Production by Upregulating microRNA-26a-5p and Deactivating the RelA and NF-κBp50 Transcription Pathways in Activated Breast Cancer Cells DOI Open Access
Aisha Farhana, Abdullah Alsrhani, Ruqaih S. Alghsham

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1404 - 1404

Published: Jan. 24, 2024

MicroRNAs (miRNAs) are involved in the modulation of pathogenic genes by binding to their mRNA sequences’ 3′ untranslated regions (3′UTR). Interleukin-6 (IL-6) is known promote cancer progression and treatment resistance. In this study, we aimed explore therapeutic effects gold nanoparticles (GNP) against IL-6 overexpression miRNA-26a-5p breast (BC) cells. GNP were synthesized using trisodium citrate method characterized through UV-Vis spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM). To predict miR-26a-5p mRNA’s 3′UTR, utilized bioinformatics algorithms. Luciferase reporter clone assays anti-miRNA-26a-5p transfection employed validate miR26a-5p 3′UTR. The activity RelA NF-κBp50 was assessed confirmed Bay 11-7082. spherical with a mean size 28.3 nm, exhibiting high stability, suitable for BC cell treatment. We found that directly regulated MCF-7 cells activated PMA. Treatment resulted inhibition secretion increase miR26a-5p. Furthermore, deactivated NF-κBp65/NF-κBp50 transcription activity. newly engineered demonstrated safety showed promise as approach reducing overexpression. suppressed deactivating upregulating expression These findings suggest have potential intervention targeting associated pathways.

Language: Английский

Citations

6
Physical Activity Decreases Inflammation and Delays Development of Obesity-Associated Pancreatic Ductal Adenocarcinoma DOI
Valentina Pita-Grisanti, Ericka Vélez-Bonet, Kaylin Chasser

et al.

Cancer Research, Journal Year: 2024, Volume and Issue: 84(18), P. 3058 - 3071

Published: May 22, 2024

Obesity is a risk factor for pancreatic ductal adenocarcinoma (PDAC), deadly disease with limited preventive strategies. Lifestyle interventions to decrease obesity represent potential approach prevent obesity-associated PDAC. In this study, we examined whether decreasing through physical activity (PA) and/or dietary changes could inflammation in humans and PDAC mice. Comparison of circulating inflammatory-associated cytokines subjects (overweight obese) before after PA intervention revealed lowered systemic inflammatory cytokines. Mice pancreatic-specific inducible KrasG12D expression were exposed during cancer initiation. mice concurrent diet-induced expression, the led lower weight gain, suppressed inflammation, delayed tumor progression, decreased proinflammatory signals adipose tissue. However, these benefits not as evident when preceded expression. Combining loss (DI-WL) progression genetically engineered mouse model, but neither alone nor combined DI-WL or chemotherapy prevented growth orthotopic models regardless status. upregulation Il15ra Adipose-specific overexpression Il15 slowed only nonobese Overall, our study suggests that can reduce delay development progression. manage therapies target loss-related molecular pathways Significance: Physical reduces induces adipose-related signaling suppress cancer, supporting management strategies developing cancer. See related commentary by Sogunro Muzumdar, p. 2935.

Language: Английский

Citations

6
Immune Cell‐Based Microrobots for Remote Magnetic Actuation, Antitumor Activity, and Medical Imaging DOI
Nihal Olcay Dogan,

Eylül Suadiye,

Paul Wrede

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: unknown

Published: June 17, 2024

Translating medical microrobots into clinics requires tracking, localization, and performing assigned tasks at target locations, which can only happen when appropriate design, actuation mechanisms, imaging systems are integrated a single microrobot. Despite this, these parameters not fully considered designing macrophage-based microrobots. This study presents living that combine macrophages with magnetic Janus particles coated FePt nanofilm for steering bacterial lipopolysaccharides stimulating in tumor-killing state. The wireless actuation, tracking techniques, antitumor abilities. These imaged under resonance optoacoustic soft-tissue-mimicking phantoms ex vivo conditions. Magnetic real-time of demonstrated static physiologically relevant flow conditions using imaging. Further, magnetically steered toward urinary bladder tumor spheroids handheld device, where the significantly reduce viability spheroids. proposed approach demonstrates proof-of-concept feasibility integrating clinic modalities cancer targeting intervention, also be implemented various other applications.

Language: Английский

Citations

6
From sweat to hope: The role of exercise‐induced extracellular vesicles in cancer prevention and treatment DOI Creative Commons
Alicia Llorente,

Agnese Brokāne,

Agata Mlynska

et al.

Journal of Extracellular Vesicles, Journal Year: 2024, Volume and Issue: 13(8)

Published: Aug. 1, 2024

Abstract The benefits of regular physical exercise on cancer prevention, as well reducing fatigue, treatment side effects and recurrence, improving quality life overall survival patients, are increasingly recognised. Initial studies showed that the concentration extracellular vesicles (EVs) increases during activity EVs carry biologically active cargo. These released by blood cells, skeletal muscle other organs involved in exercise, thus suggesting may mediate tissue crosstalk exercise. This possibility triggered a great interest study roles systemic adaptation to their potential applications prevention various diseases, including cancer. review presents exploring molecular cargo Furthermore, we discuss putative stimuli trigger EV release from cell types, biological functions impact exercise‐induced development progression. Understanding interplay between EVs, biology offer insights into novel therapeutic strategies preventive measures for

Language: Английский

Citations

6