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Modelling Immune Dynamics in Locally Advanced MSI-H/dMMR Colorectal Cancer with Neoadjuvant Pembrolizumab Treatment:
Georgio Hawi1, Peter S Kim2, Peter P Lee3
1School of Mathematics and Statistics, University of Sydney, Sydney, Australia. georgio.hawi@sydney.edu.au.
Bulletin of Mathematical Biology
|February 2, 2026
Summary
A new mathematical model simulates neoadjuvant pembrolizumab therapy for locally advanced colorectal cancer (CRC) with MSI-H/dMMR tumors. This model helps understand immune responses and provides a platform for further mechanistic investigation.
Area of Science:
- Oncology
- Computational Biology
- Immunology
Background:
- Colorectal cancer (CRC) is a leading cause of cancer death worldwide.
- MSI-H/dMMR tumors are immunogenic but can evade immune surveillance via PD-1/PD-L1.
- Pembrolizumab is an effective treatment for advanced MSI-H/dMMR CRC.
Purpose of the Study:
- To develop a minimal mathematical model of neoadjuvant pembrolizumab therapy in locally advanced MSI-H/dMMR CRC (laMCRC).
- To capture key immune dynamics involved in the therapeutic response.
- To convert the ODE model into an agent-based model (ABM) for future mechanistic investigations.
Main Methods:
- Construction of a minimal model using ordinary differential equations (ODEs).
- Calibration of ODE model parameters to experimental data.
- Conversion of the ODE model to an agent-based model (ABM).
Main Results:
- The ODE model captures essential immune dynamics in laMCRC treated with neoadjuvant pembrolizumab.
- The developed ABM preserves the dynamics of the ODE model.
- The ABM provides a flexible platform for future mechanistic studies.
Conclusions:
- Mathematical modeling, including ODEs and ABMs, is valuable for understanding complex immune responses in cancer therapy.
- The developed models offer a foundation for further research into neoadjuvant pembrolizumab efficacy in laMCRC.
- This work bridges differential equation and agent-based modeling approaches for cancer immunotherapy research.
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