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Modeling LSD1-Mediated Tumor Stagnation.

Jesse Milzman¹, Wanqiang Sheng², Doron Levy³

¹Department of Mathematics and Center for Scientific Computation and Mathematical Modeling (CSCAMM), University of Maryland, College Park, MD, 20742, USA. jmilzman@umd.edu.

Bulletin of Mathematical Biology

|January 12, 2021

Summary

This summary is machine-generated.

Lysine-specific demethylase 1 (LSD1) inhibition boosts anti-tumor T cell activity. Mathematical modeling reveals accelerated cytotoxicity but suggests it doesn't fully explain slower tumor growth in combination immunotherapies.

Keywords:

Adaptive immune response LSD1 inhibition Mathematical oncology Tumor growth Tumor-immune modeling

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Area of Science:

Immunology
Computational Biology
Oncology

Background:

Lysine-specific demethylase 1 (LSD1) is recognized as a cancer biomarker and therapeutic target.
LSD1 inhibition shows promise in reducing tumor growth and enhancing T cell infiltration.
LSD1 inhibition may synergize with PD1/PDL1 checkpoint inhibitors in cancer immunotherapy.

Purpose of the Study:

To elucidate the immunogenic effects of LSD1 inhibition on tumor growth and adaptive immune response.
To investigate the anti-tumor cytotoxicity mediated by LSD1 inhibition and T cell dynamics.
To understand the synergistic potential of LSD1 inhibition in combination immunotherapies.

Main Methods:

Development of a non-spatial delay differential equation mathematical model.
Modeling of tumor growth influenced by the adaptive immune response.
Fitting the model to data from the B16 mouse model (Sheng et al., 2018).

Main Results:

LSD1 inhibition accelerates anti-tumor cytotoxicity.
Cytotoxicity alone does not fully account for the observed slower tumor growth under LSD1 inhibition.
Evidence suggests immune mediation of the slower tumor growth effect.

Conclusions:

LSD1 inhibition enhances the immune system's ability to fight cancer.
Further research is needed to reconcile the accelerated cytotoxicity with the slower tumor growth.
Mathematical modeling provides insights into the complex interplay between LSD1 inhibition and anti-tumor immunity.