Delicate Balances in Cancer Chemotherapy: Modeling Immune Recruitment and Emergence of Systemic Drug Resistance.

Frontiers in Immunology
Anh Phong TranEduardo D. Sontag

Abstract

Metronomic chemotherapy can drastically enhance immunogenic tumor cell death. However, the mechanisms responsible are still incompletely understood. Here, we develop a mathematical model to elucidate the underlying complex interactions between tumor growth, immune system activation, and therapy-mediated immunogenic cell death. Our model is conceptually simple, yet it provides a surprisingly excellent fit to empirical data obtained from a GL261 SCID mouse glioma model treated with cyclophosphamide on a metronomic schedule. The model includes terms representing immune recruitment as well as the emergence of drug resistance during prolonged metronomic treatments. Strikingly, a single fixed set of parameters, adjusted neither for individuals nor for drug schedule, recapitulates experimental data across various drug regimens remarkably well, including treatments administered at intervals ranging from 6 to 12 days. Additionally, the model predicts peak immune activation times, rediscovering experimental data that had not been used in parameter fitting or in model construction. Notably, the validated model suggests that immunostimulatory and immunosuppressive intermediates are responsible for the observed phenomena of resistance and i...Continue Reading

References

Feb 13, 2001·Journal of Cellular Physiology·B Pasche
Oct 31, 2002·Nature Immunology·Gavin P DunnRobert D Schreiber
Dec 6, 2002·Journal of Mammary Gland Biology and Neoplasia·Elaine Y LinJeffrey W Pollard
May 29, 2003·Biochimie·S BirkléJ Aubry
Oct 8, 2003·Proceedings of the National Academy of Sciences of the United States of America·S Mangan, U Alon
Jan 2, 2004·European Journal of Cell Biology·Léon C L T van KempenLisa M Coussens
Mar 27, 2004·Proceedings of the National Academy of Sciences of the United States of America·Maria H LindInderpreet Sur
Apr 6, 2005·The Journal of Experimental Medicine·Iris LeeWayne W Hancock
Sep 6, 2005·Cancer Research·Lisette G de PillisCharles L Wiseman
Sep 13, 2005·Journal of Theoretical Biology·L G de PillisA E Radunskaya
Oct 20, 2005·Clinical Pharmacokinetics·Milly E de JongeJos H Beijnen
Sep 16, 2006·Nature Reviews. Immunology·Laurence ZitvogelGuido Kroemer
Jul 13, 2007·Journal of Bioenergetics and Biomembranes·Robert J Gillies, Robert A Gatenby
Aug 3, 2007·Molecular Cancer Therapeutics·Urban EmmeneggerRobert S Kerbel
Feb 19, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Junko YokokawaKwong Y Tsang
May 10, 2008·Seminars in Cancer Biology·Antonio SicaAlberto Mantovani
Jul 11, 2008·Trends in Cell Biology·Farbod ShojaeiNapoleone Ferrara
Jul 18, 2008·Nature Reviews. Cancer·Craig MurdochClaire E Lewis
Nov 13, 2008·Systems and Synthetic Biology·Robert EntusHerbert M Sauro
Jan 16, 2009·Apoptosis : an International Journal on Programmed Cell Death·Oliver KeppGuido Kroemer
Feb 4, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Daniele GeneraliStephen B Fox
Feb 18, 2009·Cancer Immunology, Immunotherapy : CII·Claire BanissiAntoine F Carpentier
Feb 11, 2010·Current Opinion in Immunology·Alberto Mantovani, Antonio Sica
Aug 24, 2010·Proceedings of the National Academy of Sciences of the United States of America·Oren ShovalUri Alon
Oct 21, 2010·Annals of the New York Academy of Sciences·Isabelle MartinsGuido Kroemer
Jan 21, 2011·Cancer Metastasis Reviews·Oliver KeppGuido Kroemer
May 10, 2011·Molecular Cancer Therapeutics·Raquel De SouzaMicheline Piquette-Miller
Jan 10, 2012·The Lancet Oncology·Joannes F M JacobsGosse J Adema
Feb 14, 2012·Nature Cell Biology·Yifeng XiaInder M Verma
Apr 11, 2012·Trends in Immunology·Paul A BeavisMark J Smyth
Nov 20, 2012·Annual Review of Immunology·Guido KroemerLaurence Zitvogel
Jan 29, 2013·Molecular Cell·Yuval Hart, Uri Alon
Feb 8, 2013·Cancer Immunology, Immunotherapy : CII·Gang Chen, Leisha A Emens
Mar 19, 2013·Frontiers in Pharmacology·Hiba Zahreddine, Katherine L B Borden
Mar 23, 2013·Frontiers in Immunology·Guanqiao LiMichael T Lotze
May 15, 2013·Cancer Immunology, Immunotherapy : CII·Jürgen C BeckerPer Thor Straten

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