Aging, Inflammation, and Comorbidity in Cancers—A General In Silico Study Exemplified by Myeloproliferative Malignancies
Abstract
:Simple Summary
Abstract
1. Introduction
- the dormant CHIP observation. In large screening studies of citizens, a significant fraction of the population carries the JAK2V617F mutation [17,18]. Re-examining these citizens 3–7 years later shows that the allele burden did not increase in approximately one-third of those who have not received an MPN diagnosis, while it had increased in two-thirds of these. [18] These citizens are asymptomatic regarding classical diagnostic criteria such as elevated blood cell counts, which is a severe risk of blood clots. Hence, such citizens are assumed to be in a pre-cancerous state, i.e., having CHIP. [12,18] Moreover, 38% of these are in a stable equilibrium CHIP state,
- the observation of linear increasing prevalence with age. The prevalence of JAK2V617F MPN increases approximately linearly with age [19]. However, a quantitative explanation of why is lacking. More generally, it is known that inflammatory mediators are a key feature of aging and smoldering inflammation increases the risk of cancer progression [19,20].
2. Materials and Methods
2.1. The Roskilde Immuno-Competition (RIC) Model
2.2. Dimensionless RIC Model
2.3. Data
3. Results and Discussion
3.1. The RIC Model
3.2. In Silico Dynamics of Single Disease Progression
3.3. In Silico Dynamics of Comorbidity Progression
3.4. Data Comparison with the RIC Model
3.5. Classification of VP Subtypes
3.6. The Three E’s of Immunoediting
3.7. Aging Causes Immuno-Deficiency in Cancer Development
3.8. Infection May Cause Immuno-Deficiency and Consequently Cancer Escape
3.9. Aging Explains the Observed Prevalence of JAK2V617F MPNs
3.10. Reversing Disease Progression in VPs by Naïve T-Cell Therapy
4. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
Appendix A
Parameter | |||||
Units | day−1 | cell | cell−1 day−1 | day−1 | cell−1 day−1 |
Jafari et al. [51] | 1.05 | 455 | 33.3 | 0.12 | 0.015 |
Gil et al. [52] | 0.01 | 1012 | 1012 | - | 5 × 10−11 |
Makhlouf et al. [53] | 4.31 × 10−1 | 109 | 1 × 107 | 4.12 × 10−2 | 1.1 × 10−7 |
Unni and Seshaiyer [54] | 4.31 × 10−1 | 5 × 107 | 1 × 106 | 4.12 × 10−2 | 3.5 × 10−6 |
Gurcan et al. [55] | 0.18 | 5 × 106 | 10 | 4.12 × 10−2 | 4.401 × 10−8 |
Khajanchi et al. [56] | 0.18 | 1 × 106 | - | 0.412 | - |
Pillis et al. [57] | 5.14 × 10−1 | 109 | 1 × 107 | 4.12 × 10−2 | 3.50 × 10−6 |
Kuznetsov et al. [58] | 0.18 | 5 × 108 | 7.7 × 106 | - | - |
Pillis et al. [59] | 1.5 | 1 | 1 | - | 0.5 |
Kuznetsov et al. [60] | 0.1877 | 5.319 × 102 | - | - | - |
Sajid et al. [61] | 1.15 × 10−2 | 105 | - | - | - |
Ottesen et al. [62] | 1.3 × 10−3 | 3 × 104 | - | - | - |
Our default value | 5 × 10−2 | 3 × 104 | 0.125 | 1 × 10−2 | 2 × 10−4 |
Parameters | |||||
Units | cell−1 day−1 | - | cell−1 day−1 | cell day−1 | day−1 |
Jafari et al. [51] | - | - | - | - | - |
Gil et al. [52] | - | - | 10−13 | 3 × 105 | 103 |
Makhlouf et al. [53] | - | - | 3.42 × 10−6 | 7.5 × 108 | 8.3 × 106 |
Unni and Seshaiyer [54] | - | - | 1.0 × 10−7 | 4.8 × 102 | 41.7 |
Gurcan et al. [55] | - | - | 3.422 × 10−9 | - | - |
Khajanchi et al. [56] | - | - | 2.2 × 10−8 | 1.3 × 104 | - |
Pillis et al. [57] | - | - | 1.0 × 10−7 | 1.30 × 104 | - |
Kuznetsov et al. [58] | 7.2 | 0.9997 | 0.00216 | 1.36 × 104 | 0.0412 |
Pillis et al. [59] | - | - | 1 | 0.33 | 0.2 |
Kuznetsov et al. [60] | 1.387 × 10−1 | 0.9982 | 2.496 × 10−4 | 0.1950 | 0.5010 |
Sajid et al. [61] | 10−3 | - | - | - | - |
Ottesen et al. [62] | 10−6 | - | - | - | - |
Our default value | 2.32 × 10−4 | 0.857 | 3 × 10−5 | 50.25 | 50 |
Parameter | |||||
Units | day−1 | cell | cell−1 day−1 | day−1 | cell−1 day−1 |
Almocera et al. [63] | 1.62 | 109 | 0.96 | 0.6 | 4.88 × 10−8 |
Ghosh, I. [64] | - | - | 0.52 | 0.65 | 5.74 × 10−4 |
Hernandez-Vargas et al. [65] | 8.57 | - | 1.26 × 105 | - | 1.89 × 10−6 |
Our default value | 1.15 × 10−1 | 3 × 103 | 0.933 | 1 × 10−2 | 3.7 × 10−4 |
Parameters | |||||
Units | cell−1 day−1 | - | cell−1 day−1 | cell day−1 | day−1 |
Almocera et al. [63] | - | - | - | 2 × 105 | 2 × 10−1 |
Ghosh, I. [64] | - | - | 3 × 10−7 | 0.1 | 1 |
Hernandez-Vargas et al. [65] | - | - | 10−6 | - | - |
Our default value | 5.2 × 10−4 | 0.718 | 1.5 × 10−4 | 50.25 | 50 |
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Ottesen, J.T.; Andersen, M. Aging, Inflammation, and Comorbidity in Cancers—A General In Silico Study Exemplified by Myeloproliferative Malignancies. Cancers 2023, 15, 4806. https://doi.org/10.3390/cancers15194806
Ottesen JT, Andersen M. Aging, Inflammation, and Comorbidity in Cancers—A General In Silico Study Exemplified by Myeloproliferative Malignancies. Cancers. 2023; 15(19):4806. https://doi.org/10.3390/cancers15194806
Chicago/Turabian StyleOttesen, Johnny T., and Morten Andersen. 2023. "Aging, Inflammation, and Comorbidity in Cancers—A General In Silico Study Exemplified by Myeloproliferative Malignancies" Cancers 15, no. 19: 4806. https://doi.org/10.3390/cancers15194806
APA StyleOttesen, J. T., & Andersen, M. (2023). Aging, Inflammation, and Comorbidity in Cancers—A General In Silico Study Exemplified by Myeloproliferative Malignancies. Cancers, 15(19), 4806. https://doi.org/10.3390/cancers15194806