Gastric cancer-derived exosomal miR-135b-5p impairs the function of Vγ9Vδ2 T cells by targeting specificity protein 1

Background: Gastric cancer (GC) is one of the most common malignancies worldwide. However, the biomarkers for the prognosis and diagnosis of Gastric cancer were still need. Objective: The present study aimed to evaluate whether CPZ could be a potential biomarker for GC. Method: Kaplan-Meier plotter (http://kmplot.com/analysis/) was used to determine the correlation between CPZ expression and overall survival (OS) and disease-free survival (DFS) time in GC [9]. We analyzed CPZ expression in different types of cancer and the correlation of CPZ expression with the abundance of immune infiltrates, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells, via gene modules using TIMER Database. Results: The present study identified that CPZ was overexpressed in multiple types of human cancer, including Gastric cancer. We found that overexpression of CPZ correlates to the poor prognosis of patients with STAD. Furthermore, our analyses show that immune infiltration levels and diverse immune marker sets are correlated with levels of CPZ expression in STAD. Bioinformatics analysis revealed that CPZ was involved in regulating multiple pathways, including PI3K-Akt signaling pathway, cGMP-PKG signaling pathway, Rap1 signaling pathway, TGF-beta signaling pathway, regulation of cell adhesion, extracellular matrix organization, collagen fibril organization, collagen catabolic process. Conclusion: This study for the first time provides useful information to understand the potential roles of CPZ in tumor immunology and validate it to be a potential biomarker for GC.

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Transcription factor specificity protein 1-mediated Serine/threonine kinase 39 upregulation promotes the proliferation, migration, invasion and epithelial–mesenchymal transition of hepatocellular carcinoma cells by activating the transforming growth factor-β1 /Smad2/3 pathway

Bioengineered ◽

10.1080/21655979.2021.1947939 ◽

2021 ◽

Vol 12 (1) ◽

pp. 3566-3577

Author(s):

Jing Wang ◽

Zhenyu Fan ◽

Jia Li ◽

Jingmao Yang ◽

Xiaofei Liu ◽

...

Keyword(s):

Transforming Growth Factor ◽

Epithelial Mesenchymal Transition ◽

Transforming Growth Factor Β1 ◽

Carcinoma Cells ◽

Serine Threonine Kinase ◽

Mesenchymal Transition ◽

Threonine Kinase ◽

Specificity Protein 1 ◽

Factor Specificity ◽

Specificity Protein

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764 Expansion with IL-15 increases cytotoxicity of Vγ9Vδ2 T cells and is associated with higher levels of cytotoxic molecules and T-bet

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0764 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A812-A812

Author(s):

Pia Aehnlich ◽

Per Thor Straten ◽

Ana Micaela Carnaz Simoes ◽

Signe Skadborg ◽

Gitte Olofsson

Keyword(s):

T Cells ◽

T Cell ◽

Cell Expansion ◽

Ex Vivo ◽

Adoptive Cell Therapy ◽

Hematological Cancers ◽

Cytotoxic Molecules ◽

Vγ9vδ2 T Cells ◽

T Cell Expansion

BackgroundAdoptive cell therapy (ACT) is an approved treatment option for certain hematological cancers and has also shown success for some solid cancers. Still, benefit and eligibility do not extend to all patients. ACT with Vγ9Vδ2 T cells is a promising approach to overcome this hurdle.MethodsIn this study, we explored the effect of different cytokine conditions on the expansion of Vγ9Vδ2 T cells in vitro.ResultsWe could show that Vγ9Vδ2 T cell expansion is feasible with two different cytokine conditions: (a) 1000U/ml interleukin (IL)-2 and (b) 100U/ml IL-2+100U/ml IL-15. We did not observe differences in expansion rate or Vγ9Vδ2 T cell purity between the conditions; however, IL-2/IL-15-expanded Vγ9Vδ2 T cells displayed enhanced cytotoxicity against tumor cells, also in hypoxia. While this increase in killing capacity was not reflected in phenotype, we demonstrated that IL-2/IL-15-expanded Vγ9Vδ2 T cells harbor increased amounts of perforin, granzyme B and granulysin in a resting state and release more upon activation. IL-2/IL-15-expanded Vγ9Vδ2 T cells also showed higher levels of transcription factor T-bet, which could indicate that T-bet and cytotoxic molecule levels confer the increased cytotoxicity.ConclusionsThese results advocate the inclusion of IL-15 into ex vivo Vγ9Vδ2 T cell expansion protocols in future clinical studies.

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Intratumoral CXCR5+CD8+T associates with favorable clinical outcomes and immunogenic contexture in gastric cancer

Nature Communications ◽

10.1038/s41467-021-23356-w ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Jieti Wang ◽

Ruochen Li ◽

Yifan Cao ◽

Yun Gu ◽

Hanji Fang ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

T Cells ◽

Epstein Barr Virus ◽

Effector Memory ◽

Feature Identification ◽

Barr Virus ◽

T Cell Infiltration ◽

Epstein Barr ◽

Gastric Cancer Patients

AbstractStudies that examined an association between CD8+T and prognosis in gastric cancer are inconsistent, and a distinct population of CXCR5+CD8+T associated with better overall survival has been reported among various malignancies. Here, we show that the abundance of intratumoral CXCR5+CD8+T cells is associated with better overall survival in patients with gastric cancer. Patients with TNM II + III gastric cancer with higher intratumoral CXCR5+CD8+T cell infiltration are more likely to benefit from adjuvant chemotherapy. Microsatellite-unstable and Epstein–Barr virus positive tumors are enriched with CXCR5+CD8+T cells. Gastric cancer infiltrating CXCR5+CD8+T cells represent a specific subtype of stem-like CD8+T with effector memory feature. Identification of the clinical significance and phenotype of gastric cancer infiltrating CXCR5+CD8+T provides a roadmap for patient stratification and trials of targeted therapies.

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