Potential of immunotherapies in treating hematological cancer-infection comorbidities—a mathematical modelling approach

Johnny T. Ottesen*, Morten Andersen

*Corresponding author

Publikation: Bidrag til tidsskriftTidsskriftartikelpeer review

Abstract

The immune system protects the human body against threats such as emerging cancers or infections, e.g., COVID-19. Mutated malignant cells may in many cases be controlled by the immune system to be kept at unnoticed low amount. However, a severe infection may compromise the immune system in controlling such malignant clones leading to escape and fatal cancer progression. A novel mechanism based computational model coupling cancer and infection to the adaptive immune system is presented and analyzed. The model pin-points important physiological mechanisms responsible for cancer progression and explains numerous medical observations. The progression of a cancers and the effects of treatments depend on cancer burden, the level of infection and on the efficiency of the adaptive immune system. The model exhibits bi-stability, i.e., gravitate towards one of two stable steady states: a harmless dormant state or a full-blown cancer-infection disease state. A borderline exists and if infection exceeds this for a sufficiently long period of time the cancer escapes. Early treatment is vital for remission and may control the cancer back into the stable dormant state. CAR T-cell immunotherapy is investigated by help of the model. The therapy significantly improves its efficacy in combination with antibiotics or immunomodulation.

OriginalsprogEngelsk
Artikelnummer3789
TidsskriftCancers
Vol/bind13
Udgave nummer15
ISSN2072-6694
DOI
StatusUdgivet - 1 aug. 2021

Emneord

  • Bi-stability
  • Cancer-infection comorbidity
  • Cancer-infection-immune coupling
  • CAR T-cell therapy
  • Dormant state
  • Immunotherapy
  • In silico investigation
  • Mathematical modelling
  • The three E’s of immunoediting

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