Modeling cancer immunoediting in tumor microenvironment with system characterization through the ising-model Hamiltonian

Abstract Background and objective Cancer Immunoediting (CI) describes the cellular-level interaction between tumor cells and the Immune System (IS) that takes place in the Tumor Micro-Environment (TME). CI is a highly dynamic and complex process comprising three distinct phases (Elimination, Equilib...

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Main Authors: Alfonso Rojas-Domínguez, Renato Arroyo-Duarte, Fernando Rincón-Vieyra, Matías Alvarado-Mentado
Format: Article
Language:English
Published: BMC 2022-05-01
Series:BMC Bioinformatics
Subjects:
Online Access:https://doi.org/10.1186/s12859-022-04731-w
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author Alfonso Rojas-Domínguez
Renato Arroyo-Duarte
Fernando Rincón-Vieyra
Matías Alvarado-Mentado
author_facet Alfonso Rojas-Domínguez
Renato Arroyo-Duarte
Fernando Rincón-Vieyra
Matías Alvarado-Mentado
author_sort Alfonso Rojas-Domínguez
collection DOAJ
description Abstract Background and objective Cancer Immunoediting (CI) describes the cellular-level interaction between tumor cells and the Immune System (IS) that takes place in the Tumor Micro-Environment (TME). CI is a highly dynamic and complex process comprising three distinct phases (Elimination, Equilibrium and Escape) wherein the IS can both protect against cancer development as well as, over time, promote the appearance of tumors with reduced immunogenicity. Herein we present an agent-based model for the simulation of CI in the TME, with the objective of promoting the understanding of this process. Methods Our model includes agents for tumor cells and for elements of the IS. The actions of these agents are governed by probabilistic rules, and agent recruitment (including cancer growth) is modeled via logistic functions. The system is formalized as an analogue of the Ising model from statistical mechanics to facilitate its analysis. The model was implemented in the Netlogo modeling environment and simulations were performed to verify, illustrate and characterize its operation. Results A main result from our simulations is the generation of emergent behavior in silico that is very difficult to observe directly in vivo or even in vitro. Our model is capable of generating the three phases of CI; it requires only a couple of control parameters and is robust to these. We demonstrate how our simulated system can be characterized through the Ising-model energy function, or Hamiltonian, which captures the “energy” involved in the interaction between agents and presents it in clear and distinct patterns for the different phases of CI. Conclusions The presented model is very flexible and robust, captures well the behaviors of the target system and can be easily extended to incorporate more variables such as those pertaining to different anti-cancer therapies. System characterization via the Ising-model Hamiltonian is a novel and powerful tool for a better understanding of CI and the development of more effective treatments. Since data of CI at the cellular level is very hard to procure, our hope is that tools such as this may be adopted to shed light on CI and related developing theories.
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spelling doaj.art-7482a4f3a9bf48478b990d8d4b0d157b2022-12-22T03:29:56ZengBMCBMC Bioinformatics1471-21052022-05-0123112510.1186/s12859-022-04731-wModeling cancer immunoediting in tumor microenvironment with system characterization through the ising-model HamiltonianAlfonso Rojas-Domínguez0Renato Arroyo-Duarte1Fernando Rincón-Vieyra2Matías Alvarado-Mentado3Postgraduate Studies and Research Division, Tecnológico Nacional de México – IT de LeónDepto. de Física, CUCEI, Universidad de GuadalajaraDepto. de Computación, CINVESTAV-IPNDepto. de Computación, CINVESTAV-IPNAbstract Background and objective Cancer Immunoediting (CI) describes the cellular-level interaction between tumor cells and the Immune System (IS) that takes place in the Tumor Micro-Environment (TME). CI is a highly dynamic and complex process comprising three distinct phases (Elimination, Equilibrium and Escape) wherein the IS can both protect against cancer development as well as, over time, promote the appearance of tumors with reduced immunogenicity. Herein we present an agent-based model for the simulation of CI in the TME, with the objective of promoting the understanding of this process. Methods Our model includes agents for tumor cells and for elements of the IS. The actions of these agents are governed by probabilistic rules, and agent recruitment (including cancer growth) is modeled via logistic functions. The system is formalized as an analogue of the Ising model from statistical mechanics to facilitate its analysis. The model was implemented in the Netlogo modeling environment and simulations were performed to verify, illustrate and characterize its operation. Results A main result from our simulations is the generation of emergent behavior in silico that is very difficult to observe directly in vivo or even in vitro. Our model is capable of generating the three phases of CI; it requires only a couple of control parameters and is robust to these. We demonstrate how our simulated system can be characterized through the Ising-model energy function, or Hamiltonian, which captures the “energy” involved in the interaction between agents and presents it in clear and distinct patterns for the different phases of CI. Conclusions The presented model is very flexible and robust, captures well the behaviors of the target system and can be easily extended to incorporate more variables such as those pertaining to different anti-cancer therapies. System characterization via the Ising-model Hamiltonian is a novel and powerful tool for a better understanding of CI and the development of more effective treatments. Since data of CI at the cellular level is very hard to procure, our hope is that tools such as this may be adopted to shed light on CI and related developing theories.https://doi.org/10.1186/s12859-022-04731-wTumor immune interactionCancer micro-environmentCI emergent behaviorImmunoeditingIsing energy function
spellingShingle Alfonso Rojas-Domínguez
Renato Arroyo-Duarte
Fernando Rincón-Vieyra
Matías Alvarado-Mentado
Modeling cancer immunoediting in tumor microenvironment with system characterization through the ising-model Hamiltonian
BMC Bioinformatics
Tumor immune interaction
Cancer micro-environment
CI emergent behavior
Immunoediting
Ising energy function
title Modeling cancer immunoediting in tumor microenvironment with system characterization through the ising-model Hamiltonian
title_full Modeling cancer immunoediting in tumor microenvironment with system characterization through the ising-model Hamiltonian
title_fullStr Modeling cancer immunoediting in tumor microenvironment with system characterization through the ising-model Hamiltonian
title_full_unstemmed Modeling cancer immunoediting in tumor microenvironment with system characterization through the ising-model Hamiltonian
title_short Modeling cancer immunoediting in tumor microenvironment with system characterization through the ising-model Hamiltonian
title_sort modeling cancer immunoediting in tumor microenvironment with system characterization through the ising model hamiltonian
topic Tumor immune interaction
Cancer micro-environment
CI emergent behavior
Immunoediting
Ising energy function
url https://doi.org/10.1186/s12859-022-04731-w
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