High hypoxia status in pancreatic cancer is associated with multiple hallmarks of an immunosuppressive tumor microenvironment DOI Creative Commons
Hassan Sadozai, Animesh Acharjee, Hateem Zafar Kayani

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Март 6, 2024

Introduction Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is a particularly lethal disease that often diagnosed late and refractory to forms treatment. Tumour hypoxia key hallmark PDAC purported contribute multiple facets progression such as treatment resistance, increased invasiveness, metabolic reprogramming, immunosuppression. Methods We used Buffa gene signature score profile transcriptomics datasets from cases. performed cell-type deconvolution expression profiling approaches compare immunological phenotypes cases with low high scores. further supported our findings by qPCR analyses in cell lines cultured hypoxic conditions. Results First, we demonstrated this associated tumour grade reduced survival suggesting correlated progression. Subsequently, compared immune versus (Hypoxia HI vs. Hypoxia LOW ) show levels T cells, NK cells dendritic (DC), including crucial cDC1 subset. Concomitantly, immune-related revealed tumours, mRNA for immunosuppressive molecules were notably elevated Using Random Forest machine learning approach variable selection, identified LGALS3 (Galectin-3) top status confirmed its lines. Discussion In summary, novel associations between mediators PDAC, highlighting avenues improving immunotherapy targeting these combination hypoxia-targeted drugs.

Язык: Английский

Cancer immunotherapy via synergistic coactivation of myeloid receptors CD40 and Dectin-1 DOI Open Access
Max M. Wattenberg,

Heather Coho,

Veronica M. Herrera

и другие.

Science Immunology, Год журнала: 2023, Номер 8(89)

Опубликована: Ноя. 17, 2023

Myeloid cells facilitate T cell immune evasion in cancer yet are pliable and have antitumor potential. Here, by cotargeting myeloid activation molecules, we leveraged the compartment as a therapeutic vulnerability mouse models of pancreatic cancer. solid tumors expressed receptors including pattern recognition receptor Dectin-1 TNF superfamily member CD40. In checkpoint inhibitor-resistant cancer, coactivation Dectin-1, via systemic β-glucan therapy, CD40, with agonist antibody treatment, eradicated established induced immunological memory. Antitumor activity was dependent on cDC1s but did not require classical cell-mediated cytotoxicity or blockade molecules. Rather, targeting CD40 drove IFN-γ signaling, which converged to program distinct macrophage subsets tumor responses. Thus, productive surveillance resistant inhibition can be invoked complementary signaling pathways.

Язык: Английский

Процитировано

21
CAFs Homologous Biomimetic Liposome Bearing BET Inhibitor and Pirfenidone Synergistically Promoting Antitumor Efficacy in Pancreatic Ductal Adenocarcinoma DOI Creative Commons
Zhang Yin,

Ranran Yu,

Cheng Zhao

и другие.

Advanced Science, Год журнала: 2023, Номер 11(1)

Опубликована: Ноя. 15, 2023

Abstract BRD4 is a member of the BET protein family involved in chromatin remodeling and transcriptional regulation. Several inhibitors (BETi) have entered clinical trials, demonstrating potential inducing cancer cell apoptosis tumor regression. However, resistance to BETi common solid tumors. In pancreatic cancer, it found that cancer‐associated fibroblasts (CAFs) microenvironment reduce inhibitor JQ1 sensitivity by expression. Moreover, CAFs play crucial role formation dense stromal barrier. Therefore, targeting not only enhances cells but also increases drug perfusion improves oxygen supply, thus reducing glycolysis limiting energy supply. To address this challenge, homologous mechanism utilizing activated fibroblast membrane‐coated liposomes proposed for specific precise target CAFs‐rich cancer. Additionally, TAT peptides enable penetration, delivering PFD targeted anti‐fibrotic therapy, extracellular matrix generation glycolysis, enhancing delivery sensitivity. conclusion, findings indicate tremendous CAFs‐targeting liposomal system

Язык: Английский

Процитировано

20
The power and the promise of CAR-mediated cell immunotherapy for clinical application in pancreatic cancer DOI Creative Commons
Haoyu Tang, Yizhi Cao, Yiwei Zhou

и другие.

Journal of Advanced Research, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Pancreatic cancer, referred to as the "monarch of malignancies," is a neoplastic growth mostly arising from epithelial cells pancreatic duct and acinar cells. This particular neoplasm has highly unfavorable prognosis due its marked malignancy, inconspicuous initial manifestation, challenging early detection, rapid advancement, limited survival duration. Cellular immunotherapy ex vivo culture expansion immune effector cells, granting them capacity selectively target malignant using specialized techniques. Subsequently, these modified are reintroduced into patient's organism with purpose eradicating tumor providing therapeutic intervention for cancer. Present situation: Presently, primary cellular modalities employed in treatment cancer encompass CAR T-cell therapy, TCR NK-cell therapy. Review: review provides concise overview mechanisms targets associated various cell therapies. Additionally, we will explore prospective outlook therapy context treating

Язык: Английский

Процитировано

9
Intercellular crosstalk between cancer cells and cancer-associated fibroblasts via exosomes in gastrointestinal tumors DOI Creative Commons

Longyang Cao,

Hong Ouyang

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Фев. 23, 2024

Gastrointestinal (GI) tumors are a significant global health threat, with high rates of morbidity and mortality. Exosomes contain various biologically active molecules like nucleic acids, proteins, lipids can serve as messengers for intercellular communication. They play critical roles in the exchange information between tumor cells microenvironment (TME). The TME consists mesenchymal components extracellular matrix (ECM), fibroblasts being most abundant cell type mesenchyme. Cancer-associated (CAFs) derived from normal stem that activated TME. CAFs secrete exosomes to modulate proliferation, invasion, migration, drug resistance, other biological processes tumors. Additionally, manipulate function behavior through direct cell-cell interactions. This review provides summary crosstalk GI exosomes, along potential underlying mechanisms.

Язык: Английский

Процитировано

9
High hypoxia status in pancreatic cancer is associated with multiple hallmarks of an immunosuppressive tumor microenvironment DOI Creative Commons
Hassan Sadozai, Animesh Acharjee, Hateem Zafar Kayani

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Март 6, 2024

Introduction Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is a particularly lethal disease that often diagnosed late and refractory to forms treatment. Tumour hypoxia key hallmark PDAC purported contribute multiple facets progression such as treatment resistance, increased invasiveness, metabolic reprogramming, immunosuppression. Methods We used Buffa gene signature score profile transcriptomics datasets from cases. performed cell-type deconvolution expression profiling approaches compare immunological phenotypes cases with low high scores. further supported our findings by qPCR analyses in cell lines cultured hypoxic conditions. Results First, we demonstrated this associated tumour grade reduced survival suggesting correlated progression. Subsequently, compared immune versus (Hypoxia HI vs. Hypoxia LOW ) show levels T cells, NK cells dendritic (DC), including crucial cDC1 subset. Concomitantly, immune-related revealed tumours, mRNA for immunosuppressive molecules were notably elevated Using Random Forest machine learning approach variable selection, identified LGALS3 (Galectin-3) top status confirmed its lines. Discussion In summary, novel associations between mediators PDAC, highlighting avenues improving immunotherapy targeting these combination hypoxia-targeted drugs.

Язык: Английский

Процитировано

9