A toy model of immune responses to an immunogenic cancer

By Farnoush Farahpour1; Paulo Burke2; Polly Y. Yu3; Madheshvaran S4; Tahreem Zaheer5

1. University of Duisburg-Essen 2. University of Colorado 3. Harvard University 4. Indian Institute of Science Education and Research, Pune 5. Eötvös Loránd University

A simple and generalized model of pro and anti inflammatory immune responses to an immunogenic cancer

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Version 1.0 - published on 06 Oct 2021

doi:10.21981/9J7M-V097 cite this

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Abstract

Radiotherapy (RT) is a central component of cancer treatment that potently induces tumor cell death and provides a broad contribution (about 40%) towards tumor cures. Radiation causes cell death in highly replicating tumor cells via breaking DNA double-strand breaks. Cancer-cell apoptosis after radiation treatment can trigger an immune response incorporating a complex set of molecular and cellular mechanisms. These include pro- and anti-inflammatory responses that involve several components of innate and adaptive immune systems. Using CompuCell 3D (CC3D) package, we developed a basic and generic multi-scale model of the immune response following a cytotoxic intervention in avascular tumors. The model consists of agent based modeling (ABM) for the dynamics of cellular components and PDEs for the diffusion of molecular elements. The complex phenomenon is substantially simplified in our toy model by considering a single nutrient and one damage-associated molecular pattern (DAMP).  Our model simplifies the observed biological phenomenon as follows: DAMP released by apoptotic tumor cells creates a gradient that recruits immune cells towards it. All the response mechanisms are also summarized into two representative groups of pro- and anti-inflammatory responses. The recruitment of immune cells along with the tumor cells creates a microenvironment consisting of pro- and anti-inflammatory responses whose balance determines the subsequent fate of the system, either towards complete remission or towards relapse and further tumor proliferation. Despite its simplicity, the model can reproduce some general aspects of tumor growth and immune-mediated therapy responses.

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References

Zhou J, Wang G, Chen Y, Wang H, Hua Y, Cai Z. Immunogenic cell death in cancer therapy: Present and emerging inducers. J Cell Mol Med. 2019 Aug;23(8):4854-4865. doi: 10.1111/jcmm.14356. Epub 2019 Jun 18. PMID: 31210425; PMCID: PMC6653385.

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Researchers should cite this work as follows:

  • Farnoush Farahpour, Paulo Burke, Polly Y. Yu, Madheshvaran S, Tahreem Zaheer (2021), "A toy model of immune responses to an immunogenic cancer," https://nanohub.org/resources/cc3dicdinpdac. (DOI: 10.21981/9J7M-V097).

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  1. Cancer Biology
  2. Immuno-oncology