FOXA1 enhances antitumor immunity via repressing interferon-induced PD-L1 expression in nasopharyngeal carcinoma DOI Creative Commons

Junshang Ge,

Ying Liu, Pan Chen

и другие.

Journal for ImmunoTherapy of Cancer, Год журнала: 2024, Номер 12(11), С. e010091 - e010091

Опубликована: Ноя. 1, 2024

Background Nasopharyngeal carcinoma (NPC) is a distinct subtype of head and neck cancer which prevalent in south China southeastern Asia. Consistent activation interferon (IFN) signaling, impairment T cell mediated antitumor immunity frequent NPC. Forkhead box A1 (FOXA1) one the earliest discovered pioneer factors, can open up compact chromatin structures to facilitate binding other proteins chromatin. Methods By using RNA sequencing, it was that FOXA1 suppresses signaling pathway expression related interferon-responsive genes NPC cells. The effect on programmed death-ligand 1 (PD-L1) C666-1 HK1 cells under conditions with or without IFN-γ detected through quantitative PCR (qPCR), western blot, flow cytometry. After co-culturing IFN-γ-treated vitro, apoptosis CD8 + cytotoxic cytokines were assessed by effects tumor nude mice measured tumorigenesis adoptive therapy. nuclear localization STAT1, as well colocalization STAT1 immunofluorescence, qPCR, co-immunoprecipitation experiments. Results In this study, we reported loss FOXA1, factor downregulated NPC, results IFN Repression facilitates induced PD-L1 expression, whereas overexpression exerts opposite effect. Mechanistically, interacts inhibits IRF1 promoter treatment. Co-culture FOXA1-silenced promotes vitro activated tumor-specific reduces effector molecules. Furthermore, increases therapeutic efficacy antibody (atezolizumab) against receiving T-cell Conclusions We demonstrated prevents immune evasion inhibiting Our research findings provide new insights into immunotherapeutic biomarkers targets for important clinical application death protein-1/PD-L1 antibodies

Язык: Английский

Differential impact of TIM-3 ligands on NK cell function DOI Creative Commons
Juncheng Wang,

Housaiyin Li,

Aditi Kulkarni

и другие.

Journal for ImmunoTherapy of Cancer, Год журнала: 2025, Номер 13(1), С. e010618 - e010618

Опубликована: Янв. 1, 2025

Background The transmembrane protein T-cell immunoglobulin and mucin-domain containing molecule 3 (TIM-3) is an immune checkpoint receptor that expressed by a variety of leukocyte subsets, particularly in the tumor microenvironment. An effective TIM-3-targeting therapy should account for multiple biological factors, including disease setting, specific cell types involved their varying sensitivities to four putative TIM-3 ligands (galectin-9, phosphatidylserine, high mobility group B1 carcinoembryonic antigen adhesion 1), each which engages unique binding site on receptor’s variable domain. primary objectives this study were assess prevalence function + natural killer (NK) cells patients with head neck squamous carcinoma (HNSCC), determine whether differentially affect NK functions, identify most immunosuppressive ligand, evaluate targeting ligand-mediated signaling enhances effector functions. Methods Single-cell RNA sequencing flow cytometry used prevalence, phenotypes HNSCC patient tumors blood. In vitro killing, proliferation cytokine production assays implemented modulate disruption TIM-3/ligand interaction can enhance cell-mediated antitumor mechanisms. Finally, Cancer Genome Atlas survival analysis digital spatial profiling employed potential impact etiology-associated differences outcomes. Results We demonstrate highly prevalent circulating tumor-infiltrating cells. It co-expresses CD44 marks heightened potential. Among ligands, galectin-9 consistently suppresses cytotoxicity through signaling, respectively, but promotes IFN-γ release TIM-3-dependent manner. HNSCC, elevated intratumoral gene signature associates worse outcomes, specifically those human papillomavirus (HPV) disease, potentially attributable higher levels HPV versus − patients. Conclusions Our findings underscore complex functional ligand consistent recent clinical trials suggesting alone suboptimal as immunotherapeutic approach treating malignancies.

Язык: Английский

Процитировано

2
TIMP4 serves as a novel potential prognostic biomarker for oral squamous cell carcinoma DOI Creative Commons
Lian Zhou,

Changlin Tang,

Renjie Shuai

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 21, 2025

Язык: Английский

Процитировано

0
Roles of circRNAs in viral pathogenesis DOI Creative Commons
Jiayin Liu, Yiming Wang,

Meichun Zheng

и другие.

Frontiers in Cellular and Infection Microbiology, Год журнала: 2025, Номер 15

Опубликована: Март 13, 2025

Circular RNAs (circRNAs) are a class of non-coding with covalently closed circular structure, lacking 5’-caps or 3’-poly(A) tails. They relatively conserved, highly stable, and often exhibit tissue- cell-specific production in eukaryotic cells. Based on the advances sequencing technologies bioinformatics, multiple reports have suggested that viruses other microorganisms may encode circRNA-like molecules, providing new insights into physiological pathological roles circRNAs. The innate immune system functions as body’s primary defense mechanism against viral infections. It detects pathogen-associated molecular patterns (PAMPs) activates signaling pathways to suppress replication limit their spread. CircRNAs involved regulation host play essential pathogenesis. has been shown circRNAs can regulate gene expression by acting miRNA sponges protein sponges, encoding small proteins specific cases. For example, previous studies revealed participate antiviral response through competitive endogenous RNA (ceRNA) network sponges. This review highlights research progress host- virus-encoded host-virus interactions, well potential diagnostic biomarkers therapeutic targets clinical applications.

Язык: Английский

Процитировано

0
circHIPK2 promotes malignant progression of laryngeal squamous cell carcinoma through the miR-889-3p/MCTS1/IL-6 axis DOI

Yangguang Sun,

Kai Liu, Xi Chen

и другие.

Translational Oncology, Год журнала: 2025, Номер 56, С. 102390 - 102390

Опубликована: Апрель 12, 2025

Язык: Английский

Процитировано

0
FOXA1 enhances antitumor immunity via repressing interferon-induced PD-L1 expression in nasopharyngeal carcinoma DOI Creative Commons

Junshang Ge,

Ying Liu, Pan Chen

и другие.

Journal for ImmunoTherapy of Cancer, Год журнала: 2024, Номер 12(11), С. e010091 - e010091

Опубликована: Ноя. 1, 2024

Background Nasopharyngeal carcinoma (NPC) is a distinct subtype of head and neck cancer which prevalent in south China southeastern Asia. Consistent activation interferon (IFN) signaling, impairment T cell mediated antitumor immunity frequent NPC. Forkhead box A1 (FOXA1) one the earliest discovered pioneer factors, can open up compact chromatin structures to facilitate binding other proteins chromatin. Methods By using RNA sequencing, it was that FOXA1 suppresses signaling pathway expression related interferon-responsive genes NPC cells. The effect on programmed death-ligand 1 (PD-L1) C666-1 HK1 cells under conditions with or without IFN-γ detected through quantitative PCR (qPCR), western blot, flow cytometry. After co-culturing IFN-γ-treated vitro, apoptosis CD8 + cytotoxic cytokines were assessed by effects tumor nude mice measured tumorigenesis adoptive therapy. nuclear localization STAT1, as well colocalization STAT1 immunofluorescence, qPCR, co-immunoprecipitation experiments. Results In this study, we reported loss FOXA1, factor downregulated NPC, results IFN Repression facilitates induced PD-L1 expression, whereas overexpression exerts opposite effect. Mechanistically, interacts inhibits IRF1 promoter treatment. Co-culture FOXA1-silenced promotes vitro activated tumor-specific reduces effector molecules. Furthermore, increases therapeutic efficacy antibody (atezolizumab) against receiving T-cell Conclusions We demonstrated prevents immune evasion inhibiting Our research findings provide new insights into immunotherapeutic biomarkers targets for important clinical application death protein-1/PD-L1 antibodies

Язык: Английский

Процитировано

1