Modelling the interplay between the CD4 + /CD8 + T-cell ratio and the expression of MHC-I in tumours

Christian John Hurry*, Alexander Mozeika, Alessia Annibale

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Describing the anti-tumour immune response as a series of cellular kinetic reactions from known immunological mechanisms, we create a mathematical model that shows the CD4+/CD8+ T-cell ratio, T-cell infiltration and the expression of MHC-I to be interacting factors in tumour elimination. Methods from dynamical systems theory and non-equilibrium statistical mechanics are used to model the T-cell dependent anti-tumour immune response. Our model predicts a critical level of MHC-I expression which determines whether or not the tumour escapes the immune response. This critical level of MHC-I depends on the helper/cytotoxic T-cell ratio. However, our model also suggests that the immune system is robust against small changes in this ratio. We also find that T-cell infiltration and the specificity of the intra-tumour TCR repertoire will affect the critical MHC-I expression. Our work suggests that the functional form of the time evolution of MHC-I expression may explain the qualitative behaviour of tumour growth seen in patients.

Original languageEnglish
Article number2
Number of pages28
JournalJournal of Mathematical Biology
Volume83
Issue number1
Early online date18 Jun 2021
DOIs
Publication statusPublished - Jul 2021

Keywords

  • CD4/CD8 ratio
  • Immunology
  • MHC-I
  • Statistical mechanics

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