On the fractional cell kill law governing the lysis of solid tumors

TL;DR

This paper combines simulations and mathematical analysis to explore the fractional cell kill law in tumor lysis by immune cells, proposing a new model that accounts for tumor morphology and immune effectiveness.

Contribution

It introduces a hybrid cellular automaton model that explains the saturation in the fractional cell kill law and proposes a revised law considering tumor morphology and immune response efficiency.

Findings

Tumor morphology correlates with lysis rate when CTLs are effective.

Saturation in cell kill law diminishes as immune effectiveness decreases.

A new fractional cell kill law is proposed to better describe tumor-immune interactions.

Abstract

We present in silico simulations and mathematical analyses supporting several hypotheses that explain the saturation expressed in the fractional cell kill law that governs the lysis of tumor cells by cytotoxic CD8 + T cells (CTLs). In order to give insight into the significance of the parameters appearing in such law, a hybrid cellular automaton model describing the spatio-temporal evolution of tumor growth and its interaction with the cell-mediated immune response is used. When the CTLs eradicate efficiently the tumor cells, the model predicts a correlation between the morphology of the tumors and the rate at which they are lysed. As the effectiveness of the effector cells is decreased, the saturation gradually disappears. This limit is thoroughly discussed and a new fractional cell kill is proposed.