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Abstract Recent years have seen a tremendous growth of interest in understanding the role that the adaptive immune system could play in interdicting tumor progression. In this context, it has been shown that the density of adaptive immune cells inside a solid tumor serves as a favorable prognostic marker across different types of cancer. The exact mechanisms underlying the degree of immune cell infiltration is largely unknown. Here, we quantify the temporal dynamics of the density profile of activated immune cells around a solid tumor spheroid. We propose a computational model incorporating immune cells with active, persistent movement and a proliferation rate that depends on the presence of cancer cells, and show that the model able to reproduce semi-quantitatively the experimentally measured infiltration profile. Studying the density distribution of immune cells inside a solid tumor can help us better understand immune trafficking in the tumor micro-environment, hopefully leading towards novel immunotherapeutic strategies.
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Optimal cancer evasion in a dynamic immune microenvironment generates diverse post-escape tumor antigenicity profiles
The failure of cancer treatments, including immunotherapy, continues to be a major obstacle in preventing durable remission. This failure often results from tumor evolution, both genotypic and phenotypic, away from sensitive cell states. Here, we propose a mathematical framework for studying the dynamics of adaptive immune evasion that tracks the number of tumor-associated antigens available for immune targeting. We solve for the unique optimal cancer evasion strategy using stochastic dynamic programming and demonstrate that this policy results in increased cancer evasion rates compared to a passive, fixed strategy. Our foundational model relates the likelihood and temporal dynamics of cancer evasion to features of the immune microenvironment, where tumor immunogenicity reflects a balance between cancer adaptation and host recognition. In contrast with a passive strategy, optimally adaptive evaders navigating varying selective environments result in substantially heterogeneous post-escape tumor antigenicity, giving rise to immunogenically hot and cold tumors.
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- Award ID(s):
- 2019745
- PAR ID:
- 10416784
- Date Published:
- Journal Name:
- eLife
- Volume:
- 12
- ISSN:
- 2050-084X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.7554/eLife.82786
