Potential of Immunotherapies in Treating Hematological Cancer-Infection Comorbidities-A Mathematical Modelling Approach.
CAR T-cell therapy
bi-stability
cancer-infection comorbidity
cancer-infection-immune coupling
dormant state
immunotherapy
in silico investigation
mathematical modelling
the three E’s of immunoediting
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
27 Jul 2021
27 Jul 2021
Historique:
received:
19
06
2021
revised:
08
07
2021
accepted:
23
07
2021
entrez:
7
8
2021
pubmed:
8
8
2021
medline:
8
8
2021
Statut:
epublish
Résumé
The immune system attacks threats like an emerging cancer or infections like COVID-19 but it also plays a role in dealing with autoimmune disease, e.g., inflammatory bowel diseases, and aging. Malignant cells may tend to be eradicated, to appraoch a dormant state or escape the immune system resulting in uncontrolled growth leading to cancer progression. If the immune system is busy fighting a cancer, a severe infection on top of it may compromise the immunoediting and the comorbidity may be too taxing for the immune system to control. A novel mechanism based computational model coupling a cancer-infection development to the adaptive immune system is presented and analyzed. The model maps the outcome to the underlying physiological mechanisms and agree with numerous evidence based medical observations. Progression of a cancer and the effect of treatments depend on the cancer size, the level of infection, and on the efficiency of the adaptive immune system. The model exhibits bi-stability, i.e., virtual patient trajectories gravitate towards one of two stable steady states: a dormant state or a full-blown cancer-infection disease state. An infectious threshold curve exists and if infection exceed this separatrix for sufficiently long time the cancer escapes. Thus, early treatment is vital for remission and severe infections may instigate cancer progression. CAR T-cell Immunotherapy may sufficiently control cancer progression back into a dormant state but the therapy significantly gains efficiency in combination with antibiotics or immunomodulation.
Sections du résumé
BACKGROUND
BACKGROUND
The immune system attacks threats like an emerging cancer or infections like COVID-19 but it also plays a role in dealing with autoimmune disease, e.g., inflammatory bowel diseases, and aging. Malignant cells may tend to be eradicated, to appraoch a dormant state or escape the immune system resulting in uncontrolled growth leading to cancer progression. If the immune system is busy fighting a cancer, a severe infection on top of it may compromise the immunoediting and the comorbidity may be too taxing for the immune system to control.
METHOD
METHODS
A novel mechanism based computational model coupling a cancer-infection development to the adaptive immune system is presented and analyzed. The model maps the outcome to the underlying physiological mechanisms and agree with numerous evidence based medical observations.
RESULTS AND CONCLUSIONS
CONCLUSIONS
Progression of a cancer and the effect of treatments depend on the cancer size, the level of infection, and on the efficiency of the adaptive immune system. The model exhibits bi-stability, i.e., virtual patient trajectories gravitate towards one of two stable steady states: a dormant state or a full-blown cancer-infection disease state. An infectious threshold curve exists and if infection exceed this separatrix for sufficiently long time the cancer escapes. Thus, early treatment is vital for remission and severe infections may instigate cancer progression. CAR T-cell Immunotherapy may sufficiently control cancer progression back into a dormant state but the therapy significantly gains efficiency in combination with antibiotics or immunomodulation.
Identifiants
pubmed: 34359690
pii: cancers13153789
doi: 10.3390/cancers13153789
pmc: PMC8345105
pii:
doi:
Types de publication
Journal Article
Langues
eng
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