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Natural Killer Cells Recruitment in Oncolytic Virotherapy: A Mathematical Model
Noma Susan Senekal1, Khaphetsi Joseph Mahasa2, Amina Eladdadi3
1Department of Mathematics and Computer Science, National University of Lesotho, Roma, Maseru, Lesotho. nomasenekal@gmail.com.
Bulletin of Mathematical Biology
|May 19, 2021
Summary
Optimal oncolytic virotherapy requires precise timing of natural killer (NK) cell recruitment to the tumor microenvironment (TME). This balance ensures NK cells enhance, rather than hinder, viral clearance for successful cancer treatment.
Area of Science:
- Immunology
- Mathematical Oncology
- Virology
Background:
- Natural killer (NK) cells are crucial for antiviral responses but can prematurely clear oncolytic viruses (OVs), limiting treatment efficacy.
- Understanding NK cell dynamics within the tumor microenvironment (TME) is key to optimizing oncolytic virotherapy.
Purpose of the Study:
- To investigate the impact of NK cell recruitment timing on oncolytic virotherapy outcomes.
- To identify conditions for synergistic interplay between OV-induced NK responses and viral cytopathicity.
Main Methods:
- Formulation and analysis of a mathematical model simulating tumor, OV, and NK cell interactions.
- Utilizing preclinical data to inform model parameters and dynamics.
Main Results:
- Successful oncolytic virotherapy depends on NK cell recruitment occurring at optimal, non-early or non-late, time points.
- NK cell responses augment therapy only with weak viral cytopathicity.
- Tumor growth is modulated by NK cell recruitment, and NK cell depletion increases tumor escape probability.
Conclusions:
- Oncolytic virus infection is vital for both tumor burden reduction and inducing effective NK cell responses for tumor remission.
- The developed model supports combination therapies of NK cells and OVs in oncolytic immunovirotherapy.
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