Analysing CD8+ T cell dynamics in cancer using distribution modelling

Nissrin Alachkar

University Hospital Bonn, Institute of Experimental Oncology (IEO)

"Analysing CD8+ T cell dynamics in cancer using distribution modelling"

CD8+ T cells, also known as cytotoxic T cells, play a crucial role in fighting cancer by directly targeting and eliminating tumour cells. However, prolonged exposure to tumour antigens drives these cells into exhaustion, leading to the loss of their cytotoxic functions and subsequent tumour progression. The differentiation pathway undertaken by CD8+ T cells significantly influences the efficacy and persistence of the anti-tumour response. This pathway is shaped by collective inter- and intracellular decision-making processes within a complex dynamic network, involving interactions among various immune cell populations through direct cell-cell contact or signalling molecules such as cytokines. A mechanistic understanding of CD8+ T cell differentiation into specific phenotypic subsets, as well as the complex network governing this process, is essential. To address this, we develop a quantitative, data-driven mathematical model of CD8+ T cell population dynamics in response to cancer cells, capturing cell-cell interactions, cell proliferation, and T cell differentiation into effector or exhausted subsets. We analyse multiple possible network motifs governing CD8+ T cell differentiation and proliferation. In addition, we incorporate a response-time modelling approach, where the waiting-time distribution between cell states is described by a gamma rather than an exponential distribution. This approach accounts for the system’s intracellular networks in an input-to-output formulation while keeping the model’s complexity relatively manageable for analysis.

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