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Updated: May 25, 2026
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Predictive Immune Modeling of Solid Tumors
Published on: February 25, 2020
A hybrid multiscale model for predicting CAR-T therapy outcomes in solid tumors
Mohammad R Nikmaneshi1, Lance L Munn2
1Edwin L. Steele Laboratories, Department of Radiation Oncology, Harvard Medical School and Massachusetts General Hospital, Boston, MA, 02114, USA.
Scientific Reports
|May 23, 2026
Summary
Understanding tumor microenvironment barriers is key for effective CAR-T cell immunotherapy. Our model shows collagen density and metabolic competition significantly impact T cell infiltration and tumor response.
Area of Science:
- Immunology
- Biomedical Engineering
- Computational Biology
Background:
- Tumor hotness, or T cell distribution within tumors, is crucial for immunotherapy success.
- Current strategies to enhance T cell accumulation face limitations due to poor understanding of T cell-microenvironment interactions.
Purpose of the Study:
- To develop a mechanistic physiological model of the 3D tumor microenvironment (TME).
- To evaluate CAR-T cell performance under varying environmental conditions and infusion strategies.
Main Methods:
- Integrated key vascular (rolling, adhesion, endothelial suppression) and interstitial (ECM density, metabolic competition, chemokine sensitivity) barriers into a 3D TME model.
- Simulated CAR-T cell performance across different environmental fluctuations and infusion strategies.
Main Results:
- Collagen density and metabolic competition were identified as dominant factors limiting CAR-T efficacy.
- Enhanced vascular rolling and adhesion improved infiltration but were constrained by collagen and metabolism.
- Endothelial suppression significantly reduced tumor hotness, while its alleviation improved response.
- Systemic infusion led to higher tumor hotness than intratumoral delivery.
Conclusions:
- Alleviating barriers like collagen density and metabolic competition can restore CAR-T efficacy.
- Combined infusion routes or reduced collagen density can overcome limitations in dense tumors.
- The developed mechanistic framework allows for rational optimization of CAR-T cell strategies.
