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Flow Cytometry-Based Isolation and Therapeutic Evaluation of Tumor-Infiltrating Lymphocytes in a Mouse Model of Pancreatic Cancer
Published on: January 17, 2025
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Machine learning-based integration develops a metabolism-derived consensus model for improving immunotherapy in
Yongdong Guo1, Ronglin Wang1, Jingjie Shi1
1Department of Oncology, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi, China.
Journal for Immunotherapy of Cancer
|September 22, 2023
Summary
Pancreatic cancer (PAC) immunotherapy response can be predicted by a new metabolism-related signature (MBS). This signature, linked to immune resistance and cancer stemness, offers a robust biomarker for prognosis and personalized treatment strategies.
Area of Science:
- Oncology
- Metabolic pathways
- Immunotherapy
Background:
- Pancreatic cancer (PAC) is highly malignant, with immunotherapy showing promise.
- PAC metabolic reprogramming influences the tumor microenvironment (TME) and immunotherapy outcomes.
- The metabolic landscape of PAC and its TME association are underexplored.
Purpose of the Study:
- To characterize the metabolic landscape of PAC.
- To develop a novel metabolism-related signature (MBS) for predicting immunotherapy outcomes.
- To validate MBS as a biomarker for prognosis and identify potential therapeutic targets.
Main Methods:
- Analyzed 112 metabolic pathways in 1,188 PAC patients to construct the MBS.
- Evaluated MBS predictive performance in 11 immunotherapy cohorts (bulk-RNA and single-cell).
- Validated findings using immunohistochemistry, western blotting, colony-formation assays, and an in-house cohort.
Main Results:
- MBS negatively correlates with antitumor immunity and positively with cancer stemness and immune resistance.
- MBS outperforms existing signatures in predicting immunotherapy response across multiple cohorts.
- MBS serves as a robust prognostic biomarker and identified dasatinib and epothilone B as potential treatments.
Conclusions:
- MBS offers insights into PAC immunotherapy resistance mechanisms.
- MBS is a reliable metabolism-based indicator for predicting immunotherapy response and prognosis in PAC.
- Findings support personalized treatment strategies by considering metabolic pathways and TME immune infiltration.

