Unveiling purine metabolism dysregulation orchestrated immunosuppression in advanced pancreatic cancer and concentrating on the central role of NT5E DOI Creative Commons
Junqian Zhang,

Xiaobo Zhang,

R. Wu

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 1, 2025

The dismal efficacy of immunotherapy for Pancreatic cancer (PC) can be predominantly ascribed to its distinctive cold-tumor properties. by-products purine metabolic reprogramming are extensively engaged in tumor immune modulation, influencing the functions and recruitment cells molding an microenvironment that is propitious growth. We harnessed single-cell transcriptomics spatial concurrently analyze metabolism (PM) features PC microenvironment. quantitatively appraised PM traits diverse cell subsets via scoring algorithms such as AUCell Ucell. Moreover, development cell-cell interaction analysis elucidated alterations TME induced by dysregulation. Additionally, we defined disorder characteristics patients utilized this assess phenotypes prognoses patient population. Also, identified crucial intermediate genes impact establishment immunosuppressive environment within PC, validated them through sectioning co-culture experiments. Multi - dimensional transcriptome data unique heterogeneity microenvironment, which manifested fibroblasts demonstrating higher scores TME. Cellchat revealed malignant with elevated expression were concomitantly associated frequent interactions CAFs well high ligand-receptor pairs transcription factors. Spatial further corroborated finding. Furthermore, newly constructed criteria indicated levels a lack response Finally, study singular role NT5E immunosuppression resulting from PC. CCK8 invasion experiments following model demonstrated intervention targeting could reverse augmented malignancy co-cultured CAFs. potentially key target reversing "stiff-cancer" This demonstrates disorders impinge upon exacerbate engendered progression fibrosis. Therapeutic strategies or may offer ray hope advanced PDAC.

Language: Английский

Unveiling purine metabolism dysregulation orchestrated immunosuppression in advanced pancreatic cancer and concentrating on the central role of NT5E DOI Creative Commons
Junqian Zhang,

Xiaobo Zhang,

R. Wu

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 1, 2025

The dismal efficacy of immunotherapy for Pancreatic cancer (PC) can be predominantly ascribed to its distinctive cold-tumor properties. by-products purine metabolic reprogramming are extensively engaged in tumor immune modulation, influencing the functions and recruitment cells molding an microenvironment that is propitious growth. We harnessed single-cell transcriptomics spatial concurrently analyze metabolism (PM) features PC microenvironment. quantitatively appraised PM traits diverse cell subsets via scoring algorithms such as AUCell Ucell. Moreover, development cell-cell interaction analysis elucidated alterations TME induced by dysregulation. Additionally, we defined disorder characteristics patients utilized this assess phenotypes prognoses patient population. Also, identified crucial intermediate genes impact establishment immunosuppressive environment within PC, validated them through sectioning co-culture experiments. Multi - dimensional transcriptome data unique heterogeneity microenvironment, which manifested fibroblasts demonstrating higher scores TME. Cellchat revealed malignant with elevated expression were concomitantly associated frequent interactions CAFs well high ligand-receptor pairs transcription factors. Spatial further corroborated finding. Furthermore, newly constructed criteria indicated levels a lack response Finally, study singular role NT5E immunosuppression resulting from PC. CCK8 invasion experiments following model demonstrated intervention targeting could reverse augmented malignancy co-cultured CAFs. potentially key target reversing "stiff-cancer" This demonstrates disorders impinge upon exacerbate engendered progression fibrosis. Therapeutic strategies or may offer ray hope advanced PDAC.

Language: Английский

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