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Updated: Jun 6, 2025
Flow Cytometry-Based Isolation and Therapeutic Evaluation of Tumor-Infiltrating Lymphocytes in a Mouse Model of Pancreatic Cancer
Published on: January 17, 2025
Leveraging CAR macrophages targeting c-Met for precision immunotherapy in pancreatic cancer: insights from
Lingyu Hu1, Xiaoguang Wang1, Zhengwei Song1
1Department of Surgery, The Second Affiliated Hospital of Jiaxing University, No. 1518 North Huancheng Road, Jiaxing, Zhejiang, 314000, People's Republic of China.
Background:
Pancreatic cancer is known for its poor prognosis and resistance to conventional therapies, largely due to the presence of cancer stem cells (CSCs) and aggressive angiogenesis. Effectively targeting these CSCs and associated angiogenic pathways is crucial for effective treatment. This study leverages single-cell multi-omics to explore a novel therapeutic approach involving Chimeric Antigen Receptor (CAR) macrophages engineered to target the c-Met protein on pancreatic CSCs.
Methods:
We employed single-cell RNA sequencing to analyze pancreatic cancer tissue, identifying c-Met as a key marker of CSCs. CAR macrophages were engineered using a lentiviral system to express a c-Met-specific receptor. The phagocytic efficiency of these CAR macrophages against pancreatic CSCs was assessed in vitro, along with their ability to inhibit angiogenesis. The in vivo efficacy of CAR macrophages was evaluated in a mouse model of pancreatic cancer.
Results:
CAR macrophages demonstrated high specificity for c-Met + CSCs, significantly enhancing phagocytosis and reducing the secretion of angiogenic factors such as VEGFA, FGF2, and ANGPT. In vivo, these macrophages significantly suppressed tumor growth and angiogenesis, prolonging survival in pancreatic cancer-bearing mice.
Conclusion:
CAR macrophages targeting c-Met represent a promising therapeutic strategy for pancreatic cancer, offering targeted elimination of CSCs and disruption of tumor angiogenesis. This study highlights the potential of single-cell multi-omics in guiding the development of precision immunotherapies.
Insights
Engineered Chimeric Antigen Receptor (CAR) macrophages targeting c-Met effectively eliminate pancreatic cancer stem cells (CSCs) and inhibit tumor angiogenesis, offering a promising new therapy.
Area of Science:
- Immunotherapy
- Cancer Stem Cell Biology
- Molecular Oncology
Background:
- Pancreatic cancer exhibits poor prognosis and treatment resistance due to cancer stem cells (CSCs) and angiogenesis.
- Targeting CSCs and angiogenic pathways is critical for effective pancreatic cancer treatment.
Purpose of the Study:
- To investigate a novel therapeutic strategy using Chimeric Antigen Receptor (CAR) macrophages engineered to target c-Met on pancreatic CSCs.
- To evaluate the efficacy of CAR macrophages in eliminating CSCs and inhibiting angiogenesis in pancreatic cancer.
Main Methods:
- Single-cell RNA sequencing was used to identify c-Met as a CSC marker in pancreatic cancer.
- CAR macrophages were engineered to express a c-Met-specific receptor.
- In vitro and in vivo studies assessed CAR macrophage phagocytosis, anti-angiogenic effects, and tumor suppression in a mouse model.
Main Results:
- CAR macrophages specifically targeted and phagocytosed c-Met+ CSCs.
- These macrophages reduced secretion of key angiogenic factors (VEGFA, FGF2, ANGPT).
- In vivo, CAR macrophages suppressed tumor growth, angiogenesis, and prolonged survival in mice.
Conclusions:
- CAR macrophages targeting c-Met offer a potent therapeutic strategy for pancreatic cancer by eliminating CSCs and disrupting angiogenesis.
- Single-cell multi-omics approaches can guide the development of precision immunotherapies.
