# Modelling Immune Dynamics in Locally Advanced MSI-H/dMMR Colorectal Cancer with Neoadjuvant Pembrolizumab Treatment: From Differential Equations to an Agent-Based Framework

## TL;DR

This paper models immune responses in colorectal cancer patients treated with pembrolizumab using differential equations and agent-based models.

## Contribution

The novel contribution is the development of an extensible ODE model and its conversion to an ABM for immune dynamics in laMCRC.

## Key findings

- An ODE model captures immune dynamics in pembrolizumab-treated CRC.
- The ODE model was converted to an ABM preserving its dynamics for future investigations.

## Abstract

Colorectal cancer (CRC) is the third most common malignancy worldwide, and accounts for approximately 10% of all cancers and an estimated 850,000 deaths annually. Within CRC, MSI-H/dMMR tumours are highly immunogenic due to their high mutational burden and neoantigen load, yet can evade immunosurveillance via PD-1/PD-L1-mediated signalling. Pembrolizumab, an anti-PD-1 antibody approved for unresectable or metastatic MSI-H/dMMR CRC, is emerging as a promising neoadjuvant option in the locally advanced setting, inducing rapid, deep and durable immune responses. In this work, we construct a minimal model of neoadjuvant pembrolizumab therapy in locally advanced MSI-H/dMMR CRC (laMCRC) using ordinary differential equations (ODEs), providing a highly extensible model that captures the main immune dynamics involved. On the other hand, agent-based models (ABMs) naturally capture stochasticity, interactions at an individual level, and discrete events that lie beyond the scope of differential-equation formulations. As such, we also convert our ODE model, with parameters calibrated to experimental data, to an ABM, preserving its dynamics while providing a flexible platform for future mechanistic investigation and modelling.