Spatial and single-cell transcriptomics reveal cellular heterogeneity and a novel cancer-promoting Treg cell subset in human clear-cell renal cell carcinoma DOI Creative Commons
Xiyu Song, Yumeng Zhu,

Wenwen Geng

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2025, Volume and Issue: 13(1), P. e010183 - e010183

Published: Jan. 1, 2025

Clear cell renal carcinoma (ccRCC) is the most common histologic type of RCC. However, spatial and functional heterogeneity immunosuppressive cells mechanisms by which their interactions promote immunosuppression in ccRCC have not been thoroughly investigated. To further investigate cellular regional ccRCC, we analyzed single-cell transcriptome RNA sequencing data from four patients, were obtained samples multiple regions, including tumor core, tumor-normal interface, distal normal tissue. On basis, findings investigated vitro using tissue blood 15 patients with validated broader on microarrays. In this study, revealed previously unreported subsets both stromal immune cells, as well mapped location at finer resolution. addition, clusters after removing batch effects according to six characterized gene sets, epithelial-mesenchymal transitionhigh clusters, metastatic proximal tubulehigh clusters. Importantly, identified a special regulatory T (Treg) subpopulation that has molecular characteristics terminal effector Treg but expresses cytokines, such interleukin (IL)-1β IL-18. This group stronger function was associated worse prognosis cohorts. They colocalized MRC1 + FOLR2 tumor-associated macrophages (TAMs) interface form positive feedback loop, maintaining synergistic procarcinogenic effect. traced origin IL-1β+ IL-18 can induce expression IL-1β via ERK/NF-κB pathway. We demonstrated novel cancer-promoting subset its +TAMs, provides new insight into potential therapeutic targets for ccRCC.

Language: Английский

The multiple roles of interferon regulatory factor family in health and disease DOI Creative Commons

Luyao Wang,

Yanghui Zhu,

Nan Zhang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 9, 2024

Interferon Regulatory Factors (IRFs), a family of transcription factors, profoundly influence the immune system, impacting both physiological and pathological processes. This review explores diverse functions nine mammalian IRF members, each featuring conserved domains essential for interactions with other factors cofactors. These allow IRFs to modulate broad spectrum processes, encompassing host defense, response, cell development. Conversely, their pivotal role in regulation implicates them pathophysiology various diseases, such as infectious autoimmune disorders, metabolic cancers. In this context, display dichotomous nature, functioning tumor suppressors promoters, contingent upon specific disease milieu. Post-translational modifications IRFs, including phosphorylation ubiquitination, play crucial modulating function, stability, activation. As prospective biomarkers therapeutic targets, present promising opportunities intervention. Further research is needed elucidate precise mechanisms governing regulation, potentially pioneering innovative strategies, particularly cancer treatment, where equilibrium activities paramount importance.

Language: Английский

Citations

14
IFNα-induced BST2+ tumor-associated macrophages facilitate immunosuppression and tumor growth in pancreatic cancer by ERK-CXCL7 signaling DOI Creative Commons
Chenlei Zheng, Junli Wang, Yu Zhou

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(4), P. 114088 - 114088

Published: April 1, 2024

Pancreatic ductal adenocarcinoma (PDAC) features an immunosuppressive tumor microenvironment (TME) that resists immunotherapy. Tumor-associated macrophages, abundant in the TME, modulate T cell responses. Bone marrow stromal antigen 2-positive (BST2

Language: Английский

Citations

12
Targets of tumor microenvironment for potential drug development DOI Creative Commons
Ling Zhang, Ziruoyu Wang,

Kailu Liu

et al.

MedComm – Oncology, Journal Year: 2024, Volume and Issue: 3(1)

Published: March 1, 2024

Abstract The tumor microenvironment (TME) is the ecosystem surrounding a tumor, which usually consists of nontumoral cells or components, and molecules they produce release. frequent continuous interplay between TME strongly affects development, disease progression, metastasis, responses to therapeutic interventions. As hub potential targets, has gained appreciable momentum in cancer research. Here we systematically review progress targeting as strategy develop novel antitumor drugs from immunological, stromal extracellular matrix components TME, shedding light on its complex synergies with cells. This exploration highlights transformative these elements hold refining treatment approaches. thorough examination not only accentuates TME's multifaceted nature but also positions it formidable avenue for propelling forward paradigms therapy. aims foster deeper understanding role oncogenesis exploitation advancing targeted, efficacious treatments, marking significant stride realm

Language: Английский

Citations

11
T cell exhaustion in human cancers DOI

Kuan Kang,

Xin Lin, Pan Chen

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(5), P. 189162 - 189162

Published: July 30, 2024

Language: Английский

Citations

8
Spatial and single-cell transcriptomics reveal cellular heterogeneity and a novel cancer-promoting Treg cell subset in human clear-cell renal cell carcinoma DOI Creative Commons
Xiyu Song, Yumeng Zhu,

Wenwen Geng

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2025, Volume and Issue: 13(1), P. e010183 - e010183

Published: Jan. 1, 2025

Clear cell renal carcinoma (ccRCC) is the most common histologic type of RCC. However, spatial and functional heterogeneity immunosuppressive cells mechanisms by which their interactions promote immunosuppression in ccRCC have not been thoroughly investigated. To further investigate cellular regional ccRCC, we analyzed single-cell transcriptome RNA sequencing data from four patients, were obtained samples multiple regions, including tumor core, tumor-normal interface, distal normal tissue. On basis, findings investigated vitro using tissue blood 15 patients with validated broader on microarrays. In this study, revealed previously unreported subsets both stromal immune cells, as well mapped location at finer resolution. addition, clusters after removing batch effects according to six characterized gene sets, epithelial-mesenchymal transitionhigh clusters, metastatic proximal tubulehigh clusters. Importantly, identified a special regulatory T (Treg) subpopulation that has molecular characteristics terminal effector Treg but expresses cytokines, such interleukin (IL)-1β IL-18. This group stronger function was associated worse prognosis cohorts. They colocalized MRC1 + FOLR2 tumor-associated macrophages (TAMs) interface form positive feedback loop, maintaining synergistic procarcinogenic effect. traced origin IL-1β+ IL-18 can induce expression IL-1β via ERK/NF-κB pathway. We demonstrated novel cancer-promoting subset its +TAMs, provides new insight into potential therapeutic targets for ccRCC.

Language: Английский

Citations

1