Intratumoral CD38+CD19+B cells associate with poor clinical outcomes and immunosuppression in patients with pancreatic ductal adenocarcinoma DOI Creative Commons

Heng Zhu,

Jin Xu, Wei Wang

et al.

EBioMedicine, Journal Year: 2024, Volume and Issue: 103, P. 105098 - 105098

Published: April 11, 2024

BackgroundThe widespread involvement of tumor-infiltrating B cells highlights their potential role in tumor behavior. However, cell heterogeneity PDAC remains unexplored. Studying TIL-Bs aims to identify new treatment strategies.MethodsWe performed single-cell RNA sequencing study the PDAC. The prognostic and immunologic value identified CD38+ was explored FUSCC (n = 147) TCGA 176) cohorts. Flow cytometry conducted characterize relationship between other immune cells, as well phenotypic features. In vitro vivo experiments were assess putative effect on antitumor immunity.FindingsThe presence associated with unfavorable clinicopathological features poorer overall survival (p < 0.001). Increased infiltration accompanied by reduced natural killer (NK) 0.021) increased regulatory T 0.016). Molecular profiling revealed high expression IL-10, IL-35, TGF-β, GZMB, TIM-1, CD5 CD21, confirming cell-like Co-culture demonstrated suppression NK cytotoxicity cell-derived IL-10 Finally, suggested adoptive transfer immunity administration a CD38 inhibitor hampered growth 0.001).InterpretationWe discovered an independent factor use may provide possibilities for immunotherapy.FundingThis supported National Natural Science Foundation China (U21A20374), Shanghai Municipal Technology Major Project (21JC1401500), Scientific Innovation Education Committee (2019-01-07-00-07-E00057), Special Clinical Research Health Industry Commission (No. 20204Y0265) (23ZR1479300).

Language: Английский

The GFPT2-O-GlcNAcylation-YBX1 axis promotes IL-18 secretion to regulate the tumor immune microenvironment in pancreatic cancer DOI Creative Commons
Huiru Zhang, Tianjiao Li, Xianjun Yu

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(4)

Published: April 4, 2024

Abstract The immunosuppressive microenvironment caused by several intrinsic and extrinsic mechanism has brought great challenges to the immunotherapy of pancreatic cancer. We identified GFPT2, key enzyme in hexosamine biosynthesis pathway (HBP), as an immune-related prognostic gene cancer using transcriptome sequencing further confirmed that GFPT2 promoted macrophage M2 polarization malignant phenotype HBP is a glucose metabolism leading generation uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), which utilized for protein O-GlcNAcylation. GFPT2-mediated O-GlcNAcylation played important role regulating immune microenvironment. Through cellular proteomics, we IL-18 downstream CO-IP mass spectrum, YBX1 was O-GlcNAcylated nuclear translocated Then, functioned transcription factor promote transcription. Our study elucidated relationship between metabolic cells microenvironment, might provide some insights into combination therapy vulnerability

Language: Английский

Citations

10
An emerging strategy: probiotics enhance the effectiveness of tumor immunotherapy via mediating the gut microbiome DOI Creative Commons
Shuaiming Jiang,

Wenyao Ma,

Chenchen Ma

et al.

Gut Microbes, Journal Year: 2024, Volume and Issue: 16(1)

Published: May 8, 2024

The occurrence and progression of tumors are often accompanied by disruptions in the gut microbiota. Inversely, impact microbiota on initiation cancer is becoming increasingly evident, influencing tumor microenvironment (TME) for both local distant tumors. Moreover, it even suggested to play a significant role process immunotherapy, contributing high specificity therapeutic outcomes long-term effectiveness across various types. Probiotics, with their generally positive influence microbiota, may serve as effective agents synergizing immunotherapy. They crucial activating immune system inhibit growth. In summary, this comprehensive review aims provide valuable insights into dynamic interactions between probiotics, cancer. Furthermore, we highlight recent advances mechanisms using probiotics improve By understanding these complex relationships, unlock innovative approaches diagnosis treatment while optimizing effects

Language: Английский

Citations

10
Recent Trends in Curcumin-Containing Inorganic-Based Nanoparticles Intended for In Vivo Cancer Therapy DOI Creative Commons
Douglas Dourado, Júlio Abreu Miranda, Matheus de Oliveira

et al.

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(2), P. 177 - 177

Published: Jan. 26, 2024

Curcumin is a natural compound that has been widely investigated thanks to its various biological properties, including antiproliferative. This molecule acts on different cancers such as lung, breast, pancreatic, colorectal, etc. However, the bioactive actions of curcumin have limitations when physicochemical properties compromise pharmacological potential. As therapeutic strategy against cancer, associated with inorganic nanoparticles. These nanocarriers are capable delivering and offering synergistically enhance anticancer properties. review highlights types curcumin-based nanoparticles discusses their in vivo activity models cancer.

Language: Английский

Citations

9
ALYREF-JunD-SLC7A5 axis promotes pancreatic ductal adenocarcinoma progression through epitranscriptome-metabolism reprogramming and immune evasion DOI Creative Commons
Qingbo Meng,

Yuting Xie,

Kang Sun

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Feb. 24, 2024

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a kind of tumor lacking nutrients due to its poor vascularity and desmoplasia. Recent studies have shown that cancer cells might achieve growth advantage through epitranscriptome reprogramming. However, the role m 5 C in PDAC was not fully understood. We found Aly/REF export factor (ALYREF), reader modification, overexpressed PDAC, associated with bad prognosis. In addition, ALYREF expression negatively related CD8 + T infiltration clinical samples. knockdown decreased vivo partly dependent immunity. silencing SLC7A5 subsequently inactivated mTORC1 pathway, resulting proliferation. Mechanically, specifically recognized sites JunD mRNA, maintained stabilization mRNA upregulated transcription SLC7A5. Since key transporter large neutral amino acids (LNAAs), overexpression on depleted acid microenvironment restricted function. Moreover, ALYREF-JunD-SLC7A5 axis survival TMA assays. conclusion, this research revealed relationship between transportation immune microenvironment. be novel target for metabolic vulnerability surveillance.

Language: Английский

Citations

9
Intratumoral CD38+CD19+B cells associate with poor clinical outcomes and immunosuppression in patients with pancreatic ductal adenocarcinoma DOI Creative Commons

Heng Zhu,

Jin Xu, Wei Wang

et al.

EBioMedicine, Journal Year: 2024, Volume and Issue: 103, P. 105098 - 105098

Published: April 11, 2024

BackgroundThe widespread involvement of tumor-infiltrating B cells highlights their potential role in tumor behavior. However, cell heterogeneity PDAC remains unexplored. Studying TIL-Bs aims to identify new treatment strategies.MethodsWe performed single-cell RNA sequencing study the PDAC. The prognostic and immunologic value identified CD38+ was explored FUSCC (n = 147) TCGA 176) cohorts. Flow cytometry conducted characterize relationship between other immune cells, as well phenotypic features. In vitro vivo experiments were assess putative effect on antitumor immunity.FindingsThe presence associated with unfavorable clinicopathological features poorer overall survival (p < 0.001). Increased infiltration accompanied by reduced natural killer (NK) 0.021) increased regulatory T 0.016). Molecular profiling revealed high expression IL-10, IL-35, TGF-β, GZMB, TIM-1, CD5 CD21, confirming cell-like Co-culture demonstrated suppression NK cytotoxicity cell-derived IL-10 Finally, suggested adoptive transfer immunity administration a CD38 inhibitor hampered growth 0.001).InterpretationWe discovered an independent factor use may provide possibilities for immunotherapy.FundingThis supported National Natural Science Foundation China (U21A20374), Shanghai Municipal Technology Major Project (21JC1401500), Scientific Innovation Education Committee (2019-01-07-00-07-E00057), Special Clinical Research Health Industry Commission (No. 20204Y0265) (23ZR1479300).

Language: Английский

Citations

9