Modeling bistable dynamics arising from macrophage-tumor interactions in the tumor microenvironment

Area of Science:

• Immunology
• Mathematical Biology
• Computational Oncology

Background:

• Tumor-associated macrophages (TAMs) are crucial in the tumor microenvironment (TME), originating from monocytes.
• TAMs can adopt M1 (anti-tumor) or M2 (pro-tumor) phenotypes, significantly impacting tumor progression.
• Targeting TAMs offers therapeutic potential for cancer treatment.

Purpose of the Study:

• To develop a mathematical model of tumor volume dynamics and TAM populations (naïve, M1, M2, mixed).
• To investigate the bidirectional interplay between tumor growth and macrophage polarization.
• To identify conditions for enhanced immunotherapy response through system bistability.

Main Methods:

• Developed a mathematical model simulating tumor volume and TAM populations over time.
• Incorporated bidirectional feedback between tumor development and macrophage polarization.
• Utilized numerical simulations, bifurcation analysis, and global sensitivity analysis.

Main Results:

• The model demonstrated emergent bistability in tumor-macrophage dynamics.
• Bistability indicates increased system controllability, responsiveness to perturbations, and immunotherapy sensitivity.
• Identified key parameters influencing TME and tumor dynamics through sensitivity analysis.

Conclusions:

• Mathematical modeling reveals bistability as a critical factor for effective cancer immunotherapy.
• Understanding parameter-dependent bistability can guide treatment strategies to transition from high to low tumor burden.
• This approach provides insights for developing novel therapeutic interventions targeting TAMs.