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Mathematical and Computational Models in TumorImmunology

Published online by Cambridge University Press:  06 June 2012

F. Pappalardo ,
A. Palladini ,
M. Pennisi ,
F. Castiglione  and
S. Motta
F. Pappalardo
Affiliation:
Università degli Studi di Catania, Catania, Italy
A. Palladini
Affiliation:
Università degli Studi di Catania, Catania, Italy
F. Castiglione
Affiliation:
Institute for Computing Applications "M. Picone", National Research Council of Italy, Viale Manzoni 30, 00185 Rome, Italy
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Abstract

The immune system is able to protect the host from tumor onset, and immune deficienciesare accompanied by an increased risk of cancer. Immunology is one of the fields in biologywhere the role of computational and mathematical modeling and analysis were recognized theearliest, beginning from 60s of the last century. We introduce the two most common methodsin simulating the competition among the immune system, cancers and tumor immunologystrategies: differential equations and rule-based models. Several specific implementationsare presented, describing in details how they work and how they advance or contribute thefield of tumor immunology.

Keywords

cancerstumor immunologyagent based modelsmathematical modelingvaccines
Type
Research Article
Information
Mathematical Modelling of Natural Phenomena , Volume 7 , Issue 3: Epidemiology , 2012 , pp. 186 - 203
Copyright
© EDP Sciences, 2012

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References

A.K. Abbas, A.H. Lichtman, S. Pillai. Cellular and Molecular Immunology, 6th edn. (Elsevier, 2007).
Alarcon, T., Byrne, H.M., Maini, P.K.. A multiple scale model for tumor growth, SIAM. Multiscale Model Simul., 3, (2005) 440-475. CrossRefGoogle Scholar
Antia, R., Bergstrom, C.T., Pilyugin, S.S., Kaech, S.M., Ahmed, R.. Models of CD8+ responses : 1. What is the antigen-independent proliferation program, J Theor Biol. 221, (2003) 585-598. CrossRefGoogle ScholarPubMed
Apostolopoulos, V., Osinski, C., McKenzie, I.F.. MUC1 cross-reactive Gal alpha(1,3)Gal antibodies in humans switch immune responses from cellular to humoral, Nat. Med. 4, (1998) 315-320. CrossRefGoogle ScholarPubMed
Barthlott, T., Kassiotis, G., Stockinger, B.. T cell regulation as a side effect of homeostasis and competition, J. Exp. Med. 4, (2003) 451-460. CrossRefGoogle Scholar
Bell, G.I.. Mathematical Model of Clonal Selection and Antibody Production, Nature, 228, (1970) 739-744. CrossRefGoogle ScholarPubMed
Bellomo, N., Delitala, M.. From the mathematical kinetic, and stochastic game theory to modelling mutations, onset, progression and immune competition of cancer cells, Physics of Life Reviews, 5, (2008) 183-206. CrossRefGoogle Scholar
Bocharov, G.A.. Modelling the Dynamics of LCMV Infection in Mice : Conventional and Exhaustive CTL Responses, J Theor Biol. 192(3), (1998) 283-308. CrossRefGoogle Scholar
Boggio, K., Nicoletti, G., Di Carlo, E., Cavallo, F., Landuzzi, l., Melani, C., Giovarelli, M., Rossi, I., Nanni, P., De Giovanni, C., Bouchard, P., Wolf, S., Modesti, A., Musiani, P., Lollini, P.L., Colombo, M.P., Forni, G.. Interleukin 12-mediated prevention of spontaneous mammary adenocarcinomas in two lines of Her-2/neu transgenic mice, J Exp Med 188 (1998) 589-596. CrossRefGoogle Scholar
Castiglione, F., Toschi, F., Bernaschi, M., Succi, S., Benedetti, R., Falini, B., Liso, A.. Computational modeling of the immune response to tumor antigens : implications for vaccination, J Theo Biol, 237(4) (2005) 390-400. CrossRefGoogle Scholar
Cavallo, F., Calogero, R.A., Forni, G.. Are oncoantigens suitable targets for anti-tumour therapy ?, Nat Rev Cancer 7 (2007) 707-713. CrossRefGoogle ScholarPubMed
Cavallo, F., De Giovanni, C., Nanni, P., Forni, G., Lollini, P.L.. 2011 : the immune hallmarks of cancer, Cancer Immunol Immunother 60 (2011) 319-326. CrossRefGoogle ScholarPubMed
Celada, F., Seiden, P.E.. A computer model of cellular interaction in the immune system Immunol. Today 13, (1992) 56-62. Google Scholar
Celada, F., Seiden, P.E.. Affinity Maturation and Hypermutation in a Simulation of the Humoral Response, Eur J Immunol., 26, (1996) 1350-1358. CrossRefGoogle Scholar
Chowdhury, D., Stauffer, D., Choudary, P.V.. A Unified Discrete Model of Immune Response, J Theor Biol. 145, (1990) 207-215. CrossRefGoogle ScholarPubMed
Cohen, I.R., Atlan, H.. Network Regulation of Autoimmunity : An Automation Model, J Autoimmun., 2(5), (1989) 613-625. CrossRefGoogle Scholar
De Giovanni, C., Nicoletti, G., Landuzzi, L., Astolfi, A., Croci, S., Comes, A., Ferrini, S., Meazza, R., Iezzi, M., Di Carlo, E., Musiani, P., Cavallo, F., Nanni, P., Lollini, P.L.. Immunoprevention of HER-2/neu transgenic mammary carcinoma through an interleukin 12-engineered allogeneic cell vaccine, Cancer Res 64 (2004) 4001-4009. CrossRefGoogle Scholar
Dunn, G.P., Old, L.J., Schreiber, R.D.. The immunobiology of cancer immunosurveillance and immunoediting, Immunity 21 (2004) 137-148. CrossRefGoogle Scholar
Feyerabend, S., Stevanovic, S., Gouttefangeas, C., et al. Novel multi-peptide vaccination in Hla-A2+ hormone sensitive patients with biochemical relapse of prostate cancer, Prostate, 69(9), (2009) 917-927. CrossRefGoogle Scholar
Finn, O.J.. Cancer immunology, N Engl J Med 358 (2008) 2704-2715. CrossRefGoogle ScholarPubMed
Forrest, S., Beauchemin, . Computer Immunology, Immunol Rev. 216, (2007) 176-197. CrossRefGoogle ScholarPubMed
Gatenby, R.A., Maini, P.K., Gawlinski, E.T.. Analysis of tumor as an inverse problem provides a novel theoretical framework for understanding tumor biology and therapy, Appl. Math. Letters, 15, (2002) 339-345. CrossRefGoogle Scholar
Halling-Brown, M., Pappalardo, F., Rapin, N., Zhang, P., et al. ImmunoGrid : Towards Agent-based Simulations of the Human Immune System at a Natural Scale, Philosophical Transactions A, 368, (2010) 2799-2815. CrossRefGoogle Scholar
M. Jílek, J. Ŝterzl. Model of Differentiation of Immunologically Competent Cell, in Developmental Aspects of Antibody Formation and Structure. (eds.), Academia, Prague, (1970) 963-981.
Kaufman, M., Urbain, J., Thomas, R.. Towards a Logical Analysis of the Immune Response, J Theor Biol. 114(4), (1985) 527-561. CrossRefGoogle Scholar
Kedl, R.M., Kappler, J.W., Marrack, P.. Epitope dominance, competition and T cell affinity maturation, Curr. Opin. Immunol. 15 (2003), 120-127. CrossRefGoogle Scholar
Kedl, R.M., Schaefer, B.C., Kappler, J.W., Marrack, P.. T cells down-modulate peptide-MHC complexes on APCs in vivo, Nat. Immunol. 3, (2002) 27-32. CrossRefGoogle Scholar
Kim-Schulze, S., Taback, B., Kaufman, H.L.. Cytokine therapy for cancer, Surgical Oncology Clinics of North America, 16(4), (2007) 793-818. CrossRefGoogle Scholar
Kirkali, Z., uzel, E. T.Systemic therapy of kidney cancer : tyrosine kinase inhibitors antiagiogenesis or IL-2 ?, Future Oncology, vol. 5(6), (2009) 871-888. CrossRefGoogle ScholarPubMed
Klenerman, P., Zinkernagel, R.M.. Original antigenic sin impairs cytotoxic T lymphocyte responses to viruses bearing variant epitopes, Nature 394, (1998) 482-485. Google ScholarPubMed
S. Koido, E. Hara, S. Homma, et al. Cancer vaccine by fusions of dendritic and cancer cells, Clinical and Developmental Immunology, 2009 (657369) (2009).
Kruse, C.A., Cepeda, L., Owens, B., Johnson, S.D., Stears, J., Lillehei, K.O.. Treatment of recurrent glioma with intracav- itary alloreactive cytotoxic T lymphocytes and interleukin-2, Cancer Immunology Immunotherapy, 45(2), (1997) 77-87. CrossRefGoogle Scholar
Lee, Ha Youn, Topham, D.J., Yong Park, Sung, Hollenbaugh, J., et al. Simulation and Prediction of the Adaptive Immune Response to Influenza A Virus Infection, Journal of Virology, 83(14), (2009) 7151-7165. CrossRefGoogle Scholar
Liang, S., Mozdzanowska, K., Palladino, G., Gerhard, W.. Heterosubtypic immunity to influenza type A virus in mice. Effector mechanisms and their longevity, J. Immunol. 152, (1994) 1653-1661. Google Scholar
Lin, A., Schildknecht, A., Nguyen, L.T., Ohashi, P.S.. Dendritic cells integrate signals from the tumor micro-environment to modulate immunity and tumor growth, Immunology Letters, 127(2), (2010) 77-84. CrossRefGoogle Scholar
J.F. Lynch,. A Logical Characterization of Individual-Based Models, 23rd Annual IEEE Symposium on Logic in Computer Science, (2008) 379-390.
Lollini, P.-L., Cavallo, F., Nanni, P., Forni, G.. Vaccines for tumour prevention, Nat. Rev. Cancer, 6, (2006) 204-216. CrossRefGoogle ScholarPubMed
P.L. Lollini, G. Nicoletti, L. Landuzzi, F. Cavallo, G. Forni, C. De Giovanni, P. Nanni. Vaccines and other immunological approaches for cancer immunoprevention, Curr Drug Targets (2010) Epub ahead of print.
Louzoun, Y.. The evolution of mathematical immunology, Immunological Reviews, 216, (2007) 9-20. CrossRefGoogle ScholarPubMed
P. Manneville and Al. Cellular Automata and Modeling of Complex Physical Systems, Springer Verlag Series in Physics. 46, (1989).
Mantovani, A., Allavena, P., Sica, A., Balkwill, F.. Cancer- related inflammation, Nature, 454(7203), (2008) 436-444. CrossRefGoogle ScholarPubMed
McDermott, D.F.. Immunotherapy of metastatic renal cell carcinoma, Cancer, 115(10), (2009) 2298-2305. CrossRefGoogle ScholarPubMed
M. MezÂťard, G. Parisi, M. Virasoro. Spin Glass Theory and Beyond, World Scientific, Singapore (1988).
S. Motta, F. Castiglione, P.-L. PLollini, F. Pappalardo. Modelling Vaccination Schedules for a Cancer Immunoprevention Vaccine, Immunome Research, 1 :5, (2005) doi :10.1186/1745-7580-1-5.
Nanni, P., Nicoletti, G., De Giovanni, C., Landuzzi, L., Di Carlo, E., Cavallo, F., Pupa, S.M., Rossi, I., Colombo, M.P., Ricci, C., Astolfi, A., Musiani, P., Forni, G., Lollini, P.L.. Combined allogeneic tumor cell vaccination and systemi interleukin 12 prevents mammary carcinogenesis in HER-2/neu transgenic mice, J Exp Med 194 (2001) 1195-1205. CrossRefGoogle Scholar
Nanni, P., Landuzzi, L., Nicoletti, G., De Giovanni, C., Rossi, I., Croci, S., Astolfi, A., Iezzi, M., Di Carlo, E., Musiani, P., Forni, G., Lollini, P.L.. Immunoprevention of mammary carcinoma in HER-2/neu transgenic mice is IFN-gamma and B cell dependent, J Immunol 173 (2004) 2288-2296. CrossRefGoogle ScholarPubMed
Nanni, P., Nicoletti, G., Palladini, A., Croci, S., Murgo, A., Antognoli, A., Landuzzi, L., Fabbi, M., Ferrini, S., Musiani, P., Iezzi, M., De Giovanni, C., Lollini, P.L.. Antimetastatic activity of a preventive cancer vaccine, Cancer Res., 67(22), (2007) 11037-11044. CrossRefGoogle ScholarPubMed
Neumann, A.U.. Control of the Immune Response by a Threshold Automata Model on A Lattice, Physica A : Statistical Mechanics and Its Applications, 162, (1989) 1-19. CrossRefGoogle Scholar
Novellino, L., Castelli, C., Parmiani, G.. A listing of human tumor antigens recognized by T cells, Cancer Immunol Immunother 54 (2005) 187-207. CrossRefGoogle ScholarPubMed
Palmowski, M.J., Choi, E.M., Hermans, I.F., Gilbert, S.C., Chen, J.L., Gileadi, U., Salio, M., Van Pel, A., Man, S., Bonin, E., Liljestrom, P., Dunbar, P.R., Cerundolo, V.. Competition between CTL narrows the immune response induced by prime-boost vaccination protocols, J Immunol. 168, (2002) 4391-4398. CrossRefGoogle Scholar
Palladini, A., Nicoletti, G., Pappalardo, F., Murgo, A., Grosso, V., Stivani, V., Ianzano, M.L., Antognoli, A., Croci, S., Landuzzi, L., De Giovanni, C., Nanni, P., Motta, S., Lollini, P.-L.. In silico modeling and in vivo efficacy of cancer preventive vaccinations, Cancer Research, 70(20), (2010) 7755-7763. CrossRefGoogle Scholar
Pappalardo, F., Castiglione, F., Lollini, P.-L., Motta, S.. Modelling and Simulation of Cancer Immunoprevention Vaccine, Bioinformatics, 21 :12, (2005) 2891-2897. CrossRefGoogle Scholar
Pappalardo, F., Motta, S., Lollini, P.-L., Mastriani, E.. Analysis of vaccine’s schedules using models, Cellular Immunology, 244, (2006) 137-140. CrossRefGoogle ScholarPubMed
Pappalardo, F., Halling-Brown, M.D., Rapin, N., Zhang, P., et al. ImmunoGrid, an integrative environment for large-scale simulation of the immune system for vaccine discovery, design, and optimization, Briefings in Bioinformatics, 10: 3, (2009) 330-340. CrossRefGoogle Scholar
Pappalardo, F., Pennisi, M., Castiglione, F., Motta, S.. Vaccine protocols optimization : in silico experiences, Biotechnology Advances, 28, (2010) 82-93. CrossRefGoogle ScholarPubMed
F. 1 Pappalardo, I.M. Forero, M. Pennisi, A. Palazon, I. Melero, S. Motta. SimB16 : modeling the combined anti-tumor effects of anti-CD137 monoclonal antibodies and adoptive T cell therapy against a mouse melanoma model, BMC Cancer, submitted, (2011).
Parish, C.R.. Cancer immunotherapy : the past, the present and the future, Immunology and Cell Biology, 81(2), (2003) 106-113. Google ScholarPubMed
M. Pennisi, F. Pappalardo, A. Palladini, G. Nicoletti, P.Nanni, P.-L. Lollini, S. Motta. Modeling the competition between lung metastases and the immune system using agents, BMC Bioinformatics, 11(Suppl 7) :S13, (2010) doi :10.1186/1471-2105-11-S7-S13.
M. Pennisi, C.Bianca, F. Pappalardo, S. Motta. Modeling artificial immunity against mammary carcinoma, Proceedings of the 10th International Conference on Mathematical Methods in Science and Engineering (CMMSE 2010), ISBN 978- 84-613-5510-5, (2010) 753-756.
M. Pennisi, C. Bianca, F. Pappalardo, S. Motta. Compartmental mathematical modeling of immune system - melanoma competition, Proceedings of the 10th International Conference on Mathematical Methods in Science and Engineering (CMMSE 2011), ISBN 978-84-614-6167-7, (2011) 930-934.
Perelson, A.S., Weisbuch, G.. Immunology for physicists. Reviews of Moddern Physics, 69, (1997) 1219-1267. Google Scholar
Smith, A.M., Perelson, A.S.. Influenza A virus infection kinetics : quantitative data and models, WIREs Syst Biol Med, 3(4), (2011) 429-445. CrossRefGoogle ScholarPubMed
Van Poppel, H., Joniau, S., Van Gool, S.W.. Vaccine therapy in patients with renal cell carcinoma, European Urology, 55(6), (2009) 1333-1344. CrossRefGoogle ScholarPubMed
Rice, J., Buchan, S., Stevenson, F.. Critical components of a DNA fusion vaccine able to induce protective cytotoxic T cells against a single epitope of a tumor antigen, J. Immunol. 169, (2002) 3908-3913. CrossRefGoogle Scholar
Rosenberg, S.A.. Progress in human tumour immunology and immunotherapy, Nature, 411(6835), (2001) 380-384. CrossRefGoogle Scholar
Rosenberg, S.A., Yang, J.C., Restifo, N.P.. Cancer immunotherapy : moving beyond current vaccines, Nat Med 10 (2004) 909-915. CrossRefGoogle Scholar
E. Sercarz, A.H. Coons. The Exhaustion of Specific Antibody Producing Capacity During A Secondary Response, In Mechanisms of Immunological Tolerance Conference. (eds.), Academia Prague, (1962) 78-83.
H.B. Sieburg. A Logical Dynamic Systems Approach to the Regulation of Antigen-Driven Lymphocyte Stimulation, in Theoretical Immunology : Part I. A. S. Perelson (eds.), (1992) 273-293.
Slamon, D.J., Godolphin, W., Jones, L.A., Holt, J.A., Wong, S.G., Keith, D.E., Levin, W.J., Stuart, S.G., Udove, J., Ullrich, A.. Studies of the HER-2/neu protooncogene in human breast and ovarian cancer, Science 244 (1989) 707-712. CrossRefGoogle ScholarPubMed
Smith, A.L., Wikstrom, M.E, Fazekas de St Groth, B.,. Visualizing T cell competition for peptide/MHC complexes : a specific mechanism to minimize the effect of precursor frequency, Immunity 13, (2000) 783-794. CrossRefGoogle ScholarPubMed
Stauffer, D., Pandey, R.. Immunologically Motivated Simulations of Cellular Automata, Computers in Physics. 6(4), (1992) 404. CrossRefGoogle Scholar
Ŝterzl, J.. Factors Determining the Differentiation Pathways of Immunocompetent Cells, Cold Spring Harb Symp Quant Biol. 32, (1967) 493-506. CrossRefGoogle Scholar
Stockinger, B., Barthlott, T., Kassiotis, G.. T cell regulation : a special job or everyone’s responsibility ?, Nat. Immunol. 2, (2001) 757-758. CrossRefGoogle ScholarPubMed
Ursini-Siegel, J., Schade, B., Cardiff, R.D., Muller, W.J.. Insights from transgenic mouse models of ERBB2-induced breast cancer, Nat Rev Cancer 7 (2007) 389-397. CrossRefGoogle ScholarPubMed
de Visser, K.E., Eichten, E., Coussens, L.M.. Paradoxical roles of the immune system during cancer development, Nature Reviews Cancer, 6(1), (2006) 24-37. CrossRefGoogle ScholarPubMed
Weiner, L.M., Surana, R., Wang, S.. Monoclonal anti- bodies : versatile platforms for cancer immunotherapy, Nature Reviews Immunology, 10(5), (2010) 317-327. CrossRefGoogle Scholar
Weisbuch, G., Atlan, H.. Control of the Immune Response, Journal of Physics A : Mathematical and General. 21, (1988) L189-L192. CrossRefGoogle Scholar
S. Wolfram. Theory and Applications of Cellular Automata, Redwood City, CA : Addison-Wesley (1986).
Yewdell, J.W., Bennink, J.R.. Immunodominance in major histocompatibility complex class I-restricted T lymphocyte responses, Annu. Rev. Immunol. 17, (1999) 51-88. CrossRefGoogle ScholarPubMed