A targetable developmental program co-regulates angiogenesis and immune evasion DOI Open Access
Pietro Berico, Amanda Flores Yanke, Fatemeh Van Rajabpour

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 21, 2024

ABSTRACT Ultraviolet (UV)-induced DNA mutations produce genetic drivers of cutaneous melanoma initiation and numerous neoantigens that can trigger anti-tumor immune responses in the host. Consequently, cells must rapidly evolve to evade detection by simultaneously modulating cell-autonomous epigenetic mechanisms tumor-microenvironment interactions. Angiogenesis has been implicated this process; although an increase vasculature initiates response normal tissue, solid tumors manage somehow enhance blood flow while preventing cell infiltration. By comparing expression transcription factors (TFs) across early-stage melanoma, naevi, other cancer types, we found homeodomain-containing TF HOXD13 drives a melanoblast-like developmental program, which is upregulated strongly correlated with angiogenesis exclusion. Using transcriptomics, 3D chromatin profiling, vivo models, demonstrate upregulation promotes tumor growth concomitantly enhancing suppressing T-cell orchestrates contacts between distal enhancers promoters, activating VEGFA, SEMA3A, CD73. VEGFA SEMA3A remodel CD73 elevates extracellular levels adenosine, vasodilator suppressor binds adenosine receptors (AdR) on endothelial T cells. In line these findings, HOXD13-induced advantage was significantly reversed concomitant administration VEGFR AdR inhibitors. revealing dual pro-angiogenic immunosuppressive HOXD13-CD73/VEGF gene regulatory axis, identify subset patients who might benefit from combinations inhibitors are both currently being tested clinical trials.

Language: Английский

High levels of soluble CD73 unveil resistance to BRAF inhibitors in melanoma cells DOI Open Access

Caterina Giraulo,

Lavinia Orlando,

Elva Morretta

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 177, P. 117033 - 117033

Published: June 27, 2024

Melanoma cells express high levels of CD73 that produce extracellular immunosuppressive adenosine. Changes in the expression occur response to tumor environmental factors, contributing phenotype plasticity and therapeutic resistance. Previously, we have observed can be up-regulated on surface melanoma nutritional stress. Here, explore mechanism by which release soluble under low nutrient availability whether this might affected agents targeting proto-oncogene B-Raf (BRAF). We found starved CD73, able convert AMP into adenosine, activity is abrogated selective inhibitors, APCP or PSB-12489. The from mediated matrix metalloproteinase MMP-9. Indeed, MMP-9 inhibitors significantly reduce released cells, while its increase. Of relevance, harboring an activating BRAF mutation, upon treatment with dabrafenib vemurafenib, show a strong reduction cell reduced space. Conversely, resistant membrane-bound culture medium. In summary, our data indicate cells. associated inhibitors. developing resistance increased including suggesting involved acquiring treatment.

Language: Английский

Citations

4
Innovative Immunotherapy and Its Transformative Impact on Gastric Adenocarcinoma: A Comprehensive Review of the Disease’s Origins, Epidemiology, Classification, Diagnosis, and Treatment Options DOI

Upasana Upasana,

Abhishek Kanugo, Sankha Bhattacharya

et al.

ACS Pharmacology & Translational Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

Language: Английский

Citations

0
GRHL2 suppression of NT5E/CD73 in breast cancer cells modulates CD73-mediated adenosine production and T cell recruitment DOI Creative Commons
Bircan Coban, Zi Wang, Chen‐Yi Liao

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(5), P. 109738 - 109738

Published: April 12, 2024

Language: Английский

Citations

3
TGF-β Induces the Secretion of Extracellular Vesicles Enriched with CD39 and CD73 from Cervical Cancer Cells DOI Open Access
Gabriela Molina-Castillo, Alberto Monroy, Rosario García‐Rocha

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2413 - 2413

Published: March 7, 2025

The presence of TGF-β in the tumor microenvironment cervical cancer (CC) is important for progression. In this study, we analyzed effect on expression ectonucleotidases CD39 and CD73, which are involved generation adenosine (Ado), CC cells extracellular vesicles (EVs) secreted by these cells. Treatment HeLa CaSki 72 h with recombinant human increased CD73 20 30% 40 100%, respectively. addition SB505124, an inhibitor TGF-β1 receptor, or GW4869, exosome formation release, reduced release both Furthermore, promoted secretion medium-large EVs (>130 nm) (HeLa + TGF-β/EVs) (CaSki TGF-β/EVs), (>20%) (>60%), obtained from treated had a greater capacity to generate Ado than did cultured absence factor (HeLa/EVs CaSki/EVs). These findings suggest that production TME can promote neoplastic progression through enriched CD73. Therefore, inhibition CD39+ CD73+ could be strategy treatment CC.

Language: Английский

Citations

0
Traditional Chinese medicine and its components effectively reduce resistance mediated by immune checkpoint inhibitors DOI Creative Commons
Mingxin Guo, Wentong Fang, Zhiqiang Hu

et al.

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

Published: Nov. 26, 2024

Immunotherapy has become a global focus in cancer treatment and research, with promising results from targeting immune checkpoints tumors like non-small cell lung cancer, colon melanoma. However, resistance to checkpoint inhibitors (ICIs) remains significant challenge. Traditional Chinese medicine (TCM), known for its low toxicity minimal side effects, shows promise enhancing when combined modern therapies. This study reviews recent research on ICIs mechanisms highlights TCM's potential overcoming this resistance, aiming improve efficacy while minimizing toxicity.

Language: Английский

Citations

2
The Impact of A3AR Antagonism on the Differential Expression of Chemoresistance-Related Genes in Glioblastoma Stem-like Cells DOI Creative Commons

Liuba Peñate,

Diego Carrillo-Beltrán,

Carlos Spichiger

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(5), P. 579 - 579

Published: April 30, 2024

Glioblastoma (GB) is the most aggressive and common primary malignant tumor of brain central nervous system. Without treatment, average patient survival time about six months, which can be extended to fifteen months with multimodal therapies. The chemoresistance observed in GB is, part, attributed presence a subpopulation glioblastoma-like stem cells (GSCs) that are characterized by heightened tumorigenic capacity chemoresistance. GSCs situated hypoxic niches, where they sustain promote stem-like phenotype have also been correlated high particularity generating levels extracellular adenosine (ADO), causes activation A3 receptor (A3AR) consequent increase expression activity genes related Therefore, targeting its components promising alternative for treating GB. This analysis determined were up- downregulated due A3AR blockades under both normoxic conditions. In addition, possible candidates associated positively regulated hypoxia negatively same condition analyzed. We detected three potential candidate antagonist MRS1220 conditions: LIMD1, TRIB2, TGFB1. Finally, selected markers hypoxia-inducible adenosine-producing ectonucleotidases. conclusion, we conditions generate extensive differential gene GSCs, increasing Furthermore, could regulate TGFB1, involved correlate poor prognosis, hypoxia, purinergic signaling.

Language: Английский

Citations

1
Effects of abnormal expression of CD73 on malignant phenotype of nasopharyngeal carcinoma DOI
Bin Jiang, Mingming Tang, Si Shi

et al.

Journal of Molecular Histology, Journal Year: 2023, Volume and Issue: 54(6), P. 633 - 644

Published: Oct. 24, 2023

Language: Английский

Citations

2
A targetable developmental program co-regulates angiogenesis and immune evasion DOI Open Access
Pietro Berico, Amanda Flores Yanke, Fatemeh Van Rajabpour

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 21, 2024

ABSTRACT Ultraviolet (UV)-induced DNA mutations produce genetic drivers of cutaneous melanoma initiation and numerous neoantigens that can trigger anti-tumor immune responses in the host. Consequently, cells must rapidly evolve to evade detection by simultaneously modulating cell-autonomous epigenetic mechanisms tumor-microenvironment interactions. Angiogenesis has been implicated this process; although an increase vasculature initiates response normal tissue, solid tumors manage somehow enhance blood flow while preventing cell infiltration. By comparing expression transcription factors (TFs) across early-stage melanoma, naevi, other cancer types, we found homeodomain-containing TF HOXD13 drives a melanoblast-like developmental program, which is upregulated strongly correlated with angiogenesis exclusion. Using transcriptomics, 3D chromatin profiling, vivo models, demonstrate upregulation promotes tumor growth concomitantly enhancing suppressing T-cell orchestrates contacts between distal enhancers promoters, activating VEGFA, SEMA3A, CD73. VEGFA SEMA3A remodel CD73 elevates extracellular levels adenosine, vasodilator suppressor binds adenosine receptors (AdR) on endothelial T cells. In line these findings, HOXD13-induced advantage was significantly reversed concomitant administration VEGFR AdR inhibitors. revealing dual pro-angiogenic immunosuppressive HOXD13-CD73/VEGF gene regulatory axis, identify subset patients who might benefit from combinations inhibitors are both currently being tested clinical trials.

Language: Английский

Citations

0