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Updated: Apr 10, 2026
Flow Cytometry-Based Isolation and Therapeutic Evaluation of Tumor-Infiltrating Lymphocytes in a Mouse Model of Pancreatic Cancer
Published on: January 17, 2025
Dipeptidylpeptidase 4 inhibition enhances lymphocyte trafficking, improving both naturally occurring tumor immunity
Rosa Barreira da Silva1, Melissa E Laird1, Nader Yatim1
11] Laboratory of Dendritic Cell Immunobiology, Institut Pasteur, Paris, France. [2] Inserm U818, Paris, France.
Abstract:
The success of antitumor immune responses depends on the infiltration of solid tumors by effector T cells, a process guided by chemokines. Here we show that in vivo post-translational processing of chemokines by dipeptidylpeptidase 4 (DPP4, also known as CD26) limits lymphocyte migration to sites of inflammation and tumors. Inhibition of DPP4 enzymatic activity enhanced tumor rejection by preserving biologically active CXCL10 and increasing trafficking into the tumor by lymphocytes expressing the counter-receptor CXCR3. Furthermore, DPP4 inhibition improved adjuvant-based immunotherapy, adoptive T cell transfer and checkpoint blockade. These findings provide direct in vivo evidence for control of lymphocyte trafficking via CXCL10 cleavage and support the use of DPP4 inhibitors for stabilizing biologically active forms of chemokines as a strategy to enhance tumor immunotherapy.
Insights
Dipeptidylpeptidase 4 (DPP4) enzyme activity limits T cell migration to tumors. Inhibiting DPP4 preserves active CXCL10, enhancing anti-tumor immunity and immunotherapy effectiveness.
Area of Science:
- Immunology
- Cancer Biology
- Pharmacology
Background:
- Antitumor immune responses rely on effector T cell infiltration into solid tumors.
- Chemokines are critical regulators of lymphocyte trafficking to inflammatory sites and tumors.
Purpose of the Study:
- To investigate the role of dipeptidylpeptidase 4 (DPP4) in regulating T cell migration to tumors.
- To evaluate the potential of DPP4 inhibition as a strategy to enhance cancer immunotherapy.
Main Methods:
- In vivo studies assessing chemokine processing and lymphocyte trafficking.
- Enzymatic activity assays for DPP4.
- Evaluation of tumor rejection and immunotherapy efficacy in preclinical models.
Main Results:
- DPP4 post-translational processing of chemokines limits T cell infiltration into tumors.
- Inhibition of DPP4 preserved biologically active CXCL10, enhancing T cell migration via CXCR3.
- DPP4 inhibition improved outcomes in various immunotherapy settings, including adjuvant therapy, adoptive T cell transfer, and checkpoint blockade.
Conclusions:
- DPP4 controls lymphocyte trafficking by cleaving chemokines like CXCL10.
- DPP4 inhibitors represent a promising strategy for enhancing tumor immunotherapy by stabilizing active chemokines.
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01:23Dipeptidyl Peptidase 4 Inhibitors
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