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        <pre>Noise-assisted interactions of tumor and immune cells.
Bose T1, Trimper S.
Author information

1
    Institute of Physics, Martin-Luther-University, D-06099 Halle, Germany. thomas.bose@physik.uni-halle.de

Abstract

We consider a three-state model comprising tumor cells, effector cells, and tumor-detecting cells under the influence of noises. It is demonstrated that inevitable stochastic forces existing in all three cell species are able to suppress tumor cell growth completely. Whereas the deterministic model does not reveal a stable tumor-free state, the auto-correlated noise combined with cross-correlation functions can either lead to tumor-dormant states, tumor progression, as well as to an elimination of tumor cells. The auto-correlation function exhibits a finite correlation time τ, while the cross-correlation functions shows a white-noise behavior. The evolution of each of the three kinds of cells leads to a multiplicative noise coupling. The model is investigated by means of a multivariate Fokker-Planck equation for small τ. The different behavior of the system is, above all, determined by the variation of the correlation time and the strength of the cross-correlation between tumor and tumor-detecting cells. The theoretical model is based on a biological background discussed in detail, and the results are tested using realistic parameters from experimental observations.</pre>
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      <reaction id="Formation_of_tumor_system" metaid="COPASI6" name="Formation of tumor system" reversible="false">
        <annotation>
          <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
            <rdf:Description rdf:about="#COPASI6">
	<bqmodel:hasInstance>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/ncit/C25513"/>
	</rdf:Bag>
	</bqmodel:hasInstance>
	</rdf:Description>
	
          </rdf:RDF>
          <COPASI xmlns="http://www.copasi.org/static/sbml">
            <rdf:RDF xmlns:bqmodel="http://biomodels.net/model-qualifiers/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
              <rdf:Description rdf:about="#COPASI6">
                <bqmodel:isDescribedBy rdf:resource="urn:miriam:ncit:C25513"/>
                <dcterms:created>
                  <rdf:Description>
                    <dcterms:W3CDTF>2019-12-16T09:37:42Z</dcterms:W3CDTF>
                  </rdf:Description>
                </dcterms:created>
              </rdf:Description>
            </rdf:RDF>
          </COPASI>
        </annotation>
              <listOfProducts>
          <speciesReference species="x" stoichiometry="1"/>
        </listOfProducts>
        <listOfModifiers>
          <modifierSpeciesReference species="z"/>
        </listOfModifiers>
        <kineticLaw>
          <math xmlns="http://www.w3.org/1998/Math/MathML">          
            <apply>
              <times/>
              <ci> compartment </ci>
              <apply>
                <ci> Function_for_formation_of_tumor_system </ci>
                <ci> R </ci>
                <ci> Dx </ci>
                <ci> tau </ci>
                <ci> Dz </ci>
                <ci> x </ci>
                <ci> z </ci>
              </apply>
            </apply>
          </math>
                </kineticLaw>
      </reaction>
      <reaction id="Removal_of_tumor_system" metaid="COPASI7" name="Removal of tumor system" reversible="false">
        <annotation>
          <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
            <rdf:Description rdf:about="#COPASI7">
	<bqmodel:hasInstance>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/ncit/C64914"/>
	</rdf:Bag>
	</bqmodel:hasInstance>
	</rdf:Description>
	
          </rdf:RDF>
          <COPASI xmlns="http://www.copasi.org/static/sbml">
            <rdf:RDF xmlns:bqmodel="http://biomodels.net/model-qualifiers/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
              <rdf:Description rdf:about="#COPASI7">
                <bqmodel:isDescribedBy rdf:resource="urn:miriam:ncit:C64914"/>
                <dcterms:created>
                  <rdf:Description>
                    <dcterms:W3CDTF>2019-12-16T09:43:42Z</dcterms:W3CDTF>
                  </rdf:Description>
                </dcterms:created>
              </rdf:Description>
            </rdf:RDF>
          </COPASI>
        </annotation>
              <listOfReactants>
          <speciesReference species="x" stoichiometry="1"/>
        </listOfReactants>
        <listOfModifiers>
          <modifierSpeciesReference species="y"/>
        </listOfModifiers>
        <kineticLaw>
          <math xmlns="http://www.w3.org/1998/Math/MathML">          
            <apply>
              <times/>
              <ci> compartment </ci>
              <apply>
                <ci> Function_for_removal_of_tumor_system </ci>
                <ci> x </ci>
                <ci> y </ci>
              </apply>
            </apply>
          </math>
                </kineticLaw>
      </reaction>
      <reaction id="Formation_of_effector_cell_against_tumor_cell" metaid="COPASI8" name="Formation of effector cell against tumor cell" reversible="false">
        <annotation>
          <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
            <rdf:Description rdf:about="#COPASI8">
	<bqmodel:hasInstance>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/ncit/C25513"/>
	</rdf:Bag>
	</bqmodel:hasInstance>
	</rdf:Description>
	
          </rdf:RDF>
          <COPASI xmlns="http://www.copasi.org/static/sbml">
            <rdf:RDF xmlns:bqmodel="http://biomodels.net/model-qualifiers/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
              <rdf:Description rdf:about="#COPASI8">
                <bqmodel:isDescribedBy rdf:resource="urn:miriam:ncit:C25513"/>
                <dcterms:created>
                  <rdf:Description>
                    <dcterms:W3CDTF>2019-12-16T10:23:33Z</dcterms:W3CDTF>
                  </rdf:Description>
                </dcterms:created>
              </rdf:Description>
            </rdf:RDF>
          </COPASI>
        </annotation>
              <listOfProducts>
          <speciesReference species="y" stoichiometry="1"/>
        </listOfProducts>
        <listOfModifiers>
          <modifierSpeciesReference species="z"/>
        </listOfModifiers>
        <kineticLaw>
          <math xmlns="http://www.w3.org/1998/Math/MathML">          
            <apply>
              <times/>
              <ci> compartment </ci>
              <apply>
                <ci> Function_for_Formation_of_effector_cell_against_tumor_cell </ci>
                <ci> y </ci>
                <ci> z </ci>
              </apply>
            </apply>
          </math>
                </kineticLaw>
      </reaction>
      <reaction id="Removal_of_effector_cell_functioning_against_tumor_cell" metaid="COPASI9" name="Removal of effector cell functioning against tumor cell" reversible="false">
        <annotation>
          <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
            <rdf:Description rdf:about="#COPASI9">
	<bqmodel:hasInstance>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/ncit/C64914"/>
	</rdf:Bag>
	</bqmodel:hasInstance>
	</rdf:Description>
	
          </rdf:RDF>
          <COPASI xmlns="http://www.copasi.org/static/sbml">
            <rdf:RDF xmlns:bqmodel="http://biomodels.net/model-qualifiers/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
              <rdf:Description rdf:about="#COPASI9">
                <bqmodel:isDescribedBy rdf:resource="urn:miriam:ncit:C64914"/>
                <dcterms:created>
                  <rdf:Description>
                    <dcterms:W3CDTF>2019-12-16T10:25:26Z</dcterms:W3CDTF>
                  </rdf:Description>
                </dcterms:created>
              </rdf:Description>
            </rdf:RDF>
          </COPASI>
        </annotation>
              <listOfReactants>
          <speciesReference species="y" stoichiometry="1"/>
        </listOfReactants>
        <kineticLaw>
          <math xmlns="http://www.w3.org/1998/Math/MathML">          
            <apply>
              <times/>
              <ci> compartment </ci>
              <apply>
                <ci> Function_for_Removal_of_effector_cell_functioning_against_tumor_cell </ci>
                <ci> p </ci>
                <ci> Dy </ci>
                <ci> y </ci>
              </apply>
            </apply>
          </math>
                </kineticLaw>
      </reaction>
      <reaction id="Formation_of_tumor_detecting_cell" metaid="COPASI10" name="Formation of tumor detecting cell" reversible="false">
        <annotation>
          <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
            <rdf:Description rdf:about="#COPASI10">
	<bqmodel:hasInstance>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/ncit/C25513"/>
	</rdf:Bag>
	</bqmodel:hasInstance>
	</rdf:Description>
	
          </rdf:RDF>
          <COPASI xmlns="http://www.copasi.org/static/sbml">
            <rdf:RDF xmlns:bqmodel="http://biomodels.net/model-qualifiers/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
              <rdf:Description rdf:about="#COPASI10">
                <bqmodel:isDescribedBy rdf:resource="urn:miriam:ncit:C25513"/>
                <dcterms:created>
                  <rdf:Description>
                    <dcterms:W3CDTF>2019-12-16T10:26:43Z</dcterms:W3CDTF>
                  </rdf:Description>
                </dcterms:created>
              </rdf:Description>
            </rdf:RDF>
          </COPASI>
        </annotation>
              <listOfProducts>
          <speciesReference species="z" stoichiometry="1"/>
        </listOfProducts>
        <listOfModifiers>
          <modifierSpeciesReference species="x"/>
        </listOfModifiers>
        <kineticLaw>
          <math xmlns="http://www.w3.org/1998/Math/MathML">          
            <apply>
              <times/>
              <ci> compartment </ci>
              <apply>
                <ci> Function_for_formation_of_tumor_detecting_cell </ci>
                <ci> R </ci>
                <ci> Dx </ci>
                <ci> tau </ci>
                <ci> Dz </ci>
                <ci> x </ci>
              </apply>
            </apply>
          </math>
                </kineticLaw>
      </reaction>
      <reaction id="Removal_of_tumor_detecting_cell" metaid="COPASI11" name="Removal of tumor detecting cell" reversible="false">
        <annotation>
          <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
            <rdf:Description rdf:about="#COPASI11">
	<bqmodel:hasInstance>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/ncit/C64914"/>
	</rdf:Bag>
	</bqmodel:hasInstance>
	</rdf:Description>
	
          </rdf:RDF>
          <COPASI xmlns="http://www.copasi.org/static/sbml">
            <rdf:RDF xmlns:bqmodel="http://biomodels.net/model-qualifiers/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
              <rdf:Description rdf:about="#COPASI11">
                <bqmodel:isDescribedBy rdf:resource="urn:miriam:ncit:C64914"/>
                <dcterms:created>
                  <rdf:Description>
                    <dcterms:W3CDTF>2019-12-16T10:31:29Z</dcterms:W3CDTF>
                  </rdf:Description>
                </dcterms:created>
              </rdf:Description>
            </rdf:RDF>
          </COPASI>
        </annotation>
              <listOfReactants>
          <speciesReference species="z" stoichiometry="1"/>
        </listOfReactants>
        <kineticLaw>
          <math xmlns="http://www.w3.org/1998/Math/MathML">          
            <apply>
              <times/>
              <ci> compartment </ci>
              <apply>
                <ci> Function_for_removal_of_tumor_detecting_cell </ci>
                <ci> mu </ci>
                <ci> R </ci>
                <ci> Dx </ci>
                <ci> tau </ci>
                <ci> Dz </ci>
                <ci> z </ci>
              </apply>
            </apply>
          </math>
                </kineticLaw>
      </reaction>
    </listOfReactions>
  </model>
</sbml>
