title: Tumor-immune dynamics regulated in the microenvironment inform the transient nature of immune-induced tumor dormancy.
abstract: Cancer in a host induces responses that increase the ability of the microenvironment to sustain the growing mass, for example, angiogenesis, but cancer cells can have varying sensitivities to these sustainability signals. Here, we show that these sensitivities are significant determinants of ultimate tumor fate, especially in response to treatments and immune interactions. We present a mathematical model of cancer-immune interactions that modifies generalized logistic growth with both immune-predation and immune-recruitment. The role of a growing environmental carrying capacity is discussed as a possible regulatory mechanism for tumor growth, and this regulation is shown to modify cancer-immune interactions and the possibility of achieving immune-induced tumor dormancy. This mathematical model qualitatively matches experimental observations of immune-induced tumor dormancy as it predicts dormancy as a transient period of growth that necessarily ends in either tumor elimination or tumor escape. As dormant tumors may exist asymptomatically and may be easier to treat with conventional therapy, an understanding of the mechanisms behind tumor dormancy may lead to new treatments aimed at prolonging the dormant state or converting an aggressive cancer to the dormant state.
authors.affiliation: Center of Cancer Systems Biology, GeneSys Research Institute, Tufts University School of Medicine, Boston, MA 02135, USA.
authors.forename: Kathleen P
authors.initials: KP
authors.lastname: Wilkie
authors.forename: Philip
authors.initials: P
authors.lastname: Hahnfeldt
mesh_terms: D000465:Algorithms; D000818:Animals; D002450:Cell Communication / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D008809:Mice, Inbred C3H; D018448:Models, Immunological; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D015398:Signal Transduction / Q000276:immunology; D047368:Tumor Burden / Q000276:immunology; D019139:Tumor Escape / Q000276:immunology; D059016:Tumor Microenvironment / Q000276:immunology*
references.citation: Nature. 2007 Dec 6;450(7171):903-7
references.pmid: 18026089
references.citation: Cancer Res. 1982 Nov;42(11):4740-3
references.pmid: 7127309
references.citation: Nature. 2001 Sep 13;413(6852):165-71
references.pmid: 11557981
references.citation: Bull Math Biol. 1994 Mar;56(2):295-321
references.pmid: 8186756
references.citation: Cancer Res. 2007 May 1;67(9):4491-8
references.pmid: 17483365
references.citation: Adv Exp Med Biol. 2013;734:201-34
references.pmid: 23143981
references.citation: J Natl Cancer Inst. 2006 Mar 1;98(5):316-25
references.pmid: 16507828
references.citation: Biochem J. 2012 Jan 1;441(1):77-85
references.pmid: 21943356
references.citation: Br J Cancer. 2003 Dec 15;89(12):2184-9
references.pmid: 14676792
references.citation: Science. 2002 Oct 25;298(5594):850-4
references.pmid: 12242449
references.citation: Nature. 2001 May 17;411(6835):375-9
references.pmid: 11357145
references.citation: Nature. 2004 Sep 30;431(7008):527-32
references.pmid: 15386021
references.citation: Blood. 2004 Oct 1;104(7):2124-33
references.pmid: 15191948
references.citation: Blood. 2005 Mar 15;105(6):2428-35
references.pmid: 15536145
references.citation: Nature. 2012 Feb 08;482(7385):400-4
references.pmid: 22318521
references.citation: Semin Radiat Oncol. 1993 Apr;3(2):135-143
references.pmid: 10717064
references.citation: Cancer Res. 2005 Sep 1;65(17):7950-8
references.pmid: 16140967
references.citation: J Math Biol. 1998 Sep;37(3):235-52
references.pmid: 9785481
references.citation: Biol Direct. 2012 Sep 25;7:31
references.pmid: 23009638
references.citation: Cancer Res. 1999 Oct 1;59(19):4770-5
references.pmid: 10519381
references.citation: Cancer Cell. 2008 May;13(5):394-406
references.pmid: 18455123
references.citation: Leuk Lymphoma. 2005 Mar;46(3):313-27
references.pmid: 15621821
references.citation: Nat Rev Cancer. 2006 Jan;6(1):24-37
references.pmid: 16397525
references.citation: Cold Spring Harb Perspect Biol. 2010 Nov;2(11):a003244
references.pmid: 20591988
references.citation: Phys Rev E Stat Nonlin Soft Matter Phys. 2011 Sep;84(3 Pt 1):031910
references.pmid: 22060406
references.citation: Phys Rev E Stat Nonlin Soft Matter Phys. 2010 Feb;81(2 Pt 1):021923
references.pmid: 20365611
references.citation: Annu Rev Immunol. 2004;22:329-60
references.pmid: 15032581
references.citation: Cancer Cell. 2011 May 17;19(5):640-51
references.pmid: 21575864
references.citation: J Leukoc Biol. 2008 Oct;84(4):988-93
references.pmid: 18515327
references.citation: Nat Rev Cancer. 2005 Jul;5(7):516-25
references.pmid: 15965493
references.citation: Cancer Metastasis Rev. 2010 Jun;29(2):309-16
references.pmid: 20405169
references.citation: Cell. 2010 Mar 19;140(6):883-99
references.pmid: 20303878