Endothelial autophagy blockade fosters anti-cancer immunity DOI Creative Commons
Giulia Villari, Guido Serini

EMBO Molecular Medicine, Journal Year: 2023, Volume and Issue: 16(1), P. 1 - 3

Published: Dec. 20, 2023

The discovery of immune checkpoints, consisting transmembrane ligand-receptor protein pairs that negatively regulate the CD8+ T-cell-mediated response by antigen-presenting cells (APCs) and cancer cells, has enabled a fundamental advancement therapies (Korman et al, 2022). Indeed, harnessing these homeostatic control mechanisms to their own advantage, tumor manage defend themselves from attack system, checkpoint blockade (ICB) proven be an overwhelmingly successful antitumor therapeutic approach

Language: Английский

Convergent inducers and effectors of T cell paralysis in the tumour microenvironment DOI
Douglas Hanahan, Olivier Michielin, Mikaël J. Pittet

et al.

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 24, 2024

Language: Английский

Citations

9
Advancing Immunotherapy in Pancreatic Cancer: A Brief Review of Emerging Adoptive Cell Therapies DOI Open Access

Deepak Sherpally,

Ashish Manne

Cancers, Journal Year: 2025, Volume and Issue: 17(4), P. 589 - 589

Published: Feb. 9, 2025

Pancreatic cancer has the lowest 5-year survival rate (13%) among major cancers and is third leading cause of cancer-related deaths in United States. The high lethality this attributed to its insidious onset, late-stage diagnosis, rapid progression, limited treatment options. Addressing these challenges requires a deeper understanding complex tumor microenvironment identify novel therapeutic targets. Newer approaches like adoptive cell therapy have shown remarkable success treating hematological malignancies, but their application solid tumors, particularly pancreatic cancer, still early stages development. ACT broadly involves isolating immune cells (T lymphocytes, Natural Killer cells, macrophages) from patient, followed by genetic engineering enhance mount specific anti-tumor response. Various modalities are under investigation for including chimeric antigen receptor T (CAR-T), NK (CAR-NK), tumor-infiltrating lymphocytes (TIL), T-cell (TCR)-engineered cytokine-induced killer (CIK). Major hurdles been identifying actionable antigens delivering focused cellular therapies overcome immunosuppressive dense fibrotic stroma surrounding cancer. Further studies needed explore limitations faced combination order improve clinical outcomes.

Language: Английский

Citations

1
Tumor endothelial cell autophagy is a key vascular‐immune checkpoint in melanoma DOI Creative Commons
Jelle Verhoeven, Kathryn Jacobs, Francesca Rizzollo

et al.

EMBO Molecular Medicine, Journal Year: 2023, Volume and Issue: 15(12)

Published: Nov. 27, 2023

Tumor endothelial cells (TECs) actively repress inflammatory responses and maintain an immune-excluded tumor phenotype. However, the molecular mechanisms that sustain TEC-mediated immunosuppression remain largely elusive. Here, we show autophagy ablation in TECs boosts antitumor immunity by supporting infiltration effector function of T-cells, thereby restricting melanoma growth. In melanoma-bearing mice, loss TEC leads to transcriptional expression immunostimulatory/inflammatory phenotype driven heightened NF-kB STING signaling. line, single-cell transcriptomic datasets from patients disclose enriched InflammatoryHigh /AutophagyLow correlation with clinical immunotherapy, responders exhibit increased presence inflamed vessels interfacing infiltrating CD8+ T-cells. Mechanistically, STING-dependent is not critical for immunomodulatory effects ablation, since NF-kB-driven inflammation remains functional STING/ATG5 double knockout TECs. Hence, our study identifies as a principal vascular anti-inflammatory mechanism dampening immunity.

Language: Английский

Citations

14
Unveiling the immunomodulatory dance: endothelial cells’ function and their role in non-small cell lung cancer DOI Creative Commons
Sophia Daum,

Lilith Decristoforo,

Mira Mousa

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 16, 2025

The dynamic interactions between tumor endothelial cells (TECs) and the immune microenvironment play a critical role in progression of non-small cell lung cancer (NSCLC). In general, exhibit diverse immunomodulatory properties, influencing recruitment, antigen presentation, regulation checkpoint expression. Understanding multifaceted roles TECs as well assigning specific functional hallmarks to various TEC phenotypes offer new avenues for targeted development therapeutic interventions, particularly context advanced immunotherapy anti-angiogenic treatments. This review provides insights into complex interplay system NSCLC including discussion potential optimized opportunities.

Language: Английский

Citations

0
Radiotherapy modulates autophagy to reshape the tumor immune microenvironment to enhance anti-tumor immunity in esophageal cancer DOI Creative Commons
Suna Zhou, Haihua Yang

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: unknown, P. 189302 - 189302

Published: March 1, 2025

Language: Английский

Citations

0
Senescent vascular endothelial cells promote oral squamous cell carcinoma progression through complement C3 activation DOI Creative Commons

Fangqi Jing,

Jingtian Mu,

Junjiang Liu

et al.

Archives of Oral Biology, Journal Year: 2025, Volume and Issue: unknown, P. 106242 - 106242

Published: March 1, 2025

The tumour microenvironment (TME) plays a critical role in therapeutic response and clinical outcomes cancer. Senescent stromal cells have been shown to promote progression; however, the of senescent vascular endothelial (VECs) oral squamous cell carcinoma (OSCC) remains largely unknown. In this study, we aimed explore effects potential mechanisms VECs OSCC progression. Cisplatin was used induce senescence two lines. Senescence-associated β-galactosidase (SA-β-gal) staining, immunoblotting, cycle proliferation assays, migration invasion assays were performed access development biological behavior. Additionally, RNA sequencing analysis, multiplex immunohistochemical xenograft mouse models investigate senescence-associated secretory phenotype during progression its molecular mechanisms. Cisplatin-induced exhibited senescence-related changes, including positive SA-β-gal expression upregulation p16, p21, p53, along with attenuated migration. Notably, cisplatin-induced VEC promoted proliferation, migration, by activating complement C3. Increased gene protein levels C3 observed cisplatin-treated VECs. Inhibition vitro vivo reduced invasion. induced cisplatin through activation. Targeting may offer novel strategy for treatment.

Language: Английский

Citations

0
cGAS/STING in skin melanoma: from molecular mechanisms to therapeutics DOI Creative Commons

Jafaridarabjerdi Mahin,

Xuezhu Xu, Ling Li

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Nov. 18, 2024

Language: Английский

Citations

3
Microbiome–metabolome dynamics associated with impaired glucose control and responses to lifestyle changes DOI Creative Commons
Hao Wu,

Bo‐Min Lv,

Luqian Zhi

et al.

Nature Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

Abstract Type 2 diabetes (T2D) is a complex disease shaped by genetic and environmental factors, including the gut microbiome. Recent research revealed pathophysiological heterogeneity distinct subgroups in both T2D prediabetes, prompting exploration of personalized risk factors. Using metabolomics two Swedish cohorts ( n = 1,167), we identified over 500 blood metabolites associated with impaired glucose control, approximately one-third linked to an altered Our findings metabolic disruptions microbiome–metabolome dynamics as potential mediators compromised homeostasis, illustrated interactions between Hominifimenecus microfluidus Blautia wexlerae via hippurate. Short-term lifestyle changes, for example, diet exercise, modulated microbiome-associated lifestyle-specific manner. This study suggests that axis modifiable target management, optimal health benefits achievable through combination modifications.

Language: Английский

Citations

0
Recombinant human adenovirus type 5 promotes anti-tumor immunity via inducing pyroptosis in tumor endothelial cells DOI
Zhiming Wang,

Mengkai Li,

Qingling Yang

et al.

Acta Pharmacologica Sinica, Journal Year: 2024, Volume and Issue: 45(12), P. 2646 - 2656

Published: July 19, 2024

Language: Английский

Citations

2
Sialylation-associated long non-coding RNA signature predicts the prognosis, tumor microenvironment, and immunotherapy and chemotherapy options in uterine corpus endometrial carcinoma DOI Creative Commons
Jun Chen, Tingting Wu,

Yongwen Yang

et al.

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: Sept. 11, 2024

Language: Английский

Citations

2