Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1130126 | ENA |
REPOSITORIES: ENA
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Project description:Local thermal ablation breaks immune tolerance in pacreatic cancer [RNA-seq 1]
| PRJNA884355 | ENA
Project description:Local ablation disrupts immune evasion in pancreatic cancer
| PRJNA884358 | ENA
Project description:Local ablation disrupts immune evasion in pancreatic cancer [RNA-seq 2]
| PRJNA884362 | ENA
Project description:Pancreatic cancer (PC) is a devastating disease characterised by late diagnosis, genetic neoplastic heterogeneity, poor T-cell infiltration, a highly immunosuppressive tumour microenvironment, and metastatic spreading which results in poor clinical outcomes. Surgery remains the most effective treatment, although it is limited to a few patients. Local ablative techniques, such as radiofrequency ablation (RFA), have been proposed to control PC progression in patients with nonresectable tumours. However, the impact of these therapies on promoting the activation of the immune system and eliciting an effective anti-tumour immune response remains elusive. Whether local ablative techniques could overcome resistance to immunotherapy in PC is unknown. We enrolled a cohort of patients with non-resectable locally advanced pancreatic cancer and longitudinally evaluated the impact of local thermal ablation on circulating immunological parameters. Additionally, we used cancer cell lines derived from PC transgenic mouse models to establish a preclinical platform that recapitulates systemic and localised inflammation induced by RFA in vivo. Finally, we employed this preclinical experimental platform to evaluate the efficacy of the therapeutic treatments. Thermal ablation induced a short-term inflammatory process resulting in a systemic increase in myeloid cells as well as increased plasma levels of high mobility group box 1 molecule, which correlates with a better patient outcome. We performed thermal ablative procedures in mice bearing orthotopic PC and evaluated the therapeutic efficacy of thermal treatment alone or in combination with immune checkpoint-based immunotherapy through activation of a T lymphocyte-dependent anti-tumour immune response. We demonstrated that RFA synergises with immunotherapy to restrict tumour progression, significantly improving the overall survival of PC-bearing mice. Tumour immune landscape characterisation confirmed that RFA in combination with immunotherapy supported the sculpting of an immune hostile milieu towards an effective anti-tumour milieu characterised by an increased infiltration of cytotoxic T lymphocytes in spite of CD206-expressing tumour-associated macrophages. Our study confirmed that RFA enhances immunotherapy effectiveness by breaking tumour immune tolerance and unleashing the full cytotoxic abilities of tumour-specific T-cells. Thus, RFA can circumvent the current limitations of immunotherapy in patients with pancreatic cancer.
2024-11-25 | GSE214202 | GEO
Project description:Pancreatic cancer (PC) is a devastating disease characterised by late diagnosis, genetic neoplastic heterogeneity, poor T-cell infiltration, a highly immunosuppressive tumour microenvironment, and metastatic spreading which results in poor clinical outcomes. Surgery remains the most effective treatment, although it is limited to a few patients. Local ablative techniques, such as radiofrequency ablation (RFA), have been proposed to control PC progression in patients with nonresectable tumours. However, the impact of these therapies on promoting the activation of the immune system and eliciting an effective anti-tumour immune response remains elusive. Whether local ablative techniques could overcome resistance to immunotherapy in PC is unknown. We enrolled a cohort of patients with non-resectable locally advanced pancreatic cancer and longitudinally evaluated the impact of local thermal ablation on circulating immunological parameters. Additionally, we used cancer cell lines derived from PC transgenic mouse models to establish a preclinical platform that recapitulates systemic and localised inflammation induced by RFA in vivo. Finally, we employed this preclinical experimental platform to evaluate the efficacy of the therapeutic treatments. Thermal ablation induced a short-term inflammatory process resulting in a systemic increase in myeloid cells as well as increased plasma levels of high mobility group box 1 molecule, which correlates with a better patient outcome. We performed thermal ablative procedures in mice bearing orthotopic PC and evaluated the therapeutic efficacy of thermal treatment alone or in combination with immune checkpoint-based immunotherapy through activation of a T lymphocyte-dependent anti-tumour immune response. We demonstrated that RFA synergises with immunotherapy to restrict tumour progression, significantly improving the overall survival of PC-bearing mice. Tumour immune landscape characterisation confirmed that RFA in combination with immunotherapy supported the sculpting of an immune hostile milieu towards an effective anti-tumour milieu characterised by an increased infiltration of cytotoxic T lymphocytes in spite of CD206-expressing tumour-associated macrophages. Our study confirmed that RFA enhances immunotherapy effectiveness by breaking tumour immune tolerance and unleashing the full cytotoxic abilities of tumour-specific T-cells. Thus, RFA can circumvent the current limitations of immunotherapy in patients with pancreatic cancer.
2024-11-25 | GSE214205 | GEO
Project description:Current chemotherapy or immunotherapy regimens for pancreatic cancer are limited. Although minimally invasive irreversible electroporation (IRE) ablation is a promising option for unresectable pancreatic cancers, the typical immunosuppressive tumour microenvironment promotes immune evasion and rapid tumour recurrence. Thus, triggering efficient amplification of endogenous adaptive antitumour immunity is critical for improving immunotherapy after ablation therapy. Here, we developed a hydrogel microsphere vaccine as an immune amplifier for post-ablation cancer immunotherapy. The vaccine acts as a general immune amplifier to trigger a rocket-like amplification of the cDC1-mediated antigen cross-presentation cascade, resulting in dramatic amplification of the antitumour immunity of endogenous CD8+ T cells. We also showed that the hydrogel microsphere vaccine promoted the transformation of pancreatic cancer from "cold" to "hot" tumours in a safe and efficient manner, significantly increased the survival of mice bearing orthotopic pancreatic tumours, and induced strong systemic antitumour immunity, which inhibited the growth of distant metastases.
2023-05-22 | GSE215417 | GEO
Project description:The paper describes a model on the size of pancreatic tumour.
Created by COPASI 4.25 (Build 207)
This model is described in the article:
Modeling Pancreatic Cancer Dynamics with Immunotherapy
Xiaochuan Hu, Guoyi Ke and Sophia R.-J. Jang
Bulletin of Mathematical Biology (2019) 81:1885–1915
Abstract:
We develop a mathematical model of pancreatic cancer that includes pancreatic cancer cells, pancreatic stellate cells, effector cells and tumor-promoting and tumor- suppressing cytokines to investigate the effects of immunotherapies on patient survival. The model is first validated using the survival data of two clinical trials. Local sen- sitivity analysis of the parameters indicates there exists a critical activation rate of pro-tumor cytokines beyond which the cancer can be eradicated if four adoptive trans- fers of immune cells are applied. Optimal control theory is explored as a potential tool for searching the best adoptive cellular immunotherapies. Combined immunother- apies between adoptive ex vivo expanded immune cells and TGF-β inhibition by siRNA treatments are investigated. This study concludes that mono-immunotherapy is unlikely to control the pancreatic cancer and combined immunotherapies between anti-TGF-β and adoptive transfers of immune cells can prolong patient survival. We show through numerical explorations that how these two types of immunotherapies are scheduled is important to survival. Applying TGF-β inhibition first followed by adoptive immune cell transfers can yield better survival outcomes.
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2024-09-02 | BIOMD0000000744 | BioModels
Project description:Molecular analysis of precursor lesions in familial pancreatic cancer
2025-01-24 | E-GEOD-43288 | ExpressionAtlas
Project description:Multiple Salivary Biomarkers for Early Detection of Pancreatic Cancer
2025-01-24 | E-GEOD-14245 | ExpressionAtlas
Project description:RIP1 Kinase Drives Macrophage-Mediated Adaptive Immune Tolerance in Pancreatic Cancer
| PRJNA437634 | ENA