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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Mathematical model reveals how regulating the three phases of T-cell response could counteract immune evasion</title><author><name sortKey="Lorenzi, Tommaso" sort="Lorenzi, Tommaso" uniqKey="Lorenzi T" first="Tommaso" last="Lorenzi">Tommaso Lorenzi</name><affiliation><nlm:aff id="au1"><institution>Centre de Mathématiques et de Leurs Applications, ENS Cachan, CNRS</institution><addr-line>Cachan Cedex, France</addr-line></nlm:aff></affiliation></author><author><name sortKey="Chisholm, Rebecca H" sort="Chisholm, Rebecca H" uniqKey="Chisholm R" first="Rebecca H" last="Chisholm">Rebecca H. Chisholm</name><affiliation><nlm:aff id="au2"><institution>School of Biotechnology and Biomolecular Sciences, University of New South Wales</institution><addr-line>Sydney, Australia</addr-line></nlm:aff></affiliation></author><author><name sortKey="Melensi, Matteo" sort="Melensi, Matteo" uniqKey="Melensi M" first="Matteo" last="Melensi">Matteo Melensi</name><affiliation><nlm:aff id="au3"><institution>Department of Health Sciences, A. Avogadro Università del Piemonte Orientale</institution><addr-line>Novara, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Lorz, Alexander" sort="Lorz, Alexander" uniqKey="Lorz A" first="Alexander" last="Lorz">Alexander Lorz</name><affiliation><nlm:aff id="au4"><institution>MAMBA Team, INRIA-Paris-Rocquencourt</institution><addr-line>Le Chesnay Cedex, France</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="au5"><institution>Laboratoire Jacques-Louis Lions, Sorbonne Universités, UPMC Univ Paris 06, UMR 7598</institution><addr-line>Paris, France</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="au6"><institution>Laboratoire Jacques-Louis Lions, CNRS, UMR 7598</institution><addr-line>Paris, France</addr-line></nlm:aff></affiliation></author><author><name sortKey="Delitala, Marcello" sort="Delitala, Marcello" uniqKey="Delitala M" first="Marcello" last="Delitala">Marcello Delitala</name><affiliation><nlm:aff id="au7"><institution>Department of Mathematical Sciences, Politecnico di Torino</institution><addr-line>Torino, Italy</addr-line></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26119966</idno><idno type="pmc">4582968</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4582968</idno><idno type="RBID">PMC:4582968</idno><idno type="doi">10.1111/imm.12500</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000192</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000192</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Mathematical model reveals how regulating the three phases of T-cell response could counteract immune evasion</title><author><name sortKey="Lorenzi, Tommaso" sort="Lorenzi, Tommaso" uniqKey="Lorenzi T" first="Tommaso" last="Lorenzi">Tommaso Lorenzi</name><affiliation><nlm:aff id="au1"><institution>Centre de Mathématiques et de Leurs Applications, ENS Cachan, CNRS</institution><addr-line>Cachan Cedex, France</addr-line></nlm:aff></affiliation></author><author><name sortKey="Chisholm, Rebecca H" sort="Chisholm, Rebecca H" uniqKey="Chisholm R" first="Rebecca H" last="Chisholm">Rebecca H. Chisholm</name><affiliation><nlm:aff id="au2"><institution>School of Biotechnology and Biomolecular Sciences, University of New South Wales</institution><addr-line>Sydney, Australia</addr-line></nlm:aff></affiliation></author><author><name sortKey="Melensi, Matteo" sort="Melensi, Matteo" uniqKey="Melensi M" first="Matteo" last="Melensi">Matteo Melensi</name><affiliation><nlm:aff id="au3"><institution>Department of Health Sciences, A. Avogadro Università del Piemonte Orientale</institution><addr-line>Novara, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Lorz, Alexander" sort="Lorz, Alexander" uniqKey="Lorz A" first="Alexander" last="Lorz">Alexander Lorz</name><affiliation><nlm:aff id="au4"><institution>MAMBA Team, INRIA-Paris-Rocquencourt</institution><addr-line>Le Chesnay Cedex, France</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="au5"><institution>Laboratoire Jacques-Louis Lions, Sorbonne Universités, UPMC Univ Paris 06, UMR 7598</institution><addr-line>Paris, France</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="au6"><institution>Laboratoire Jacques-Louis Lions, CNRS, UMR 7598</institution><addr-line>Paris, France</addr-line></nlm:aff></affiliation></author><author><name sortKey="Delitala, Marcello" sort="Delitala, Marcello" uniqKey="Delitala M" first="Marcello" last="Delitala">Marcello Delitala</name><affiliation><nlm:aff id="au7"><institution>Department of Mathematical Sciences, Politecnico di Torino</institution><addr-line>Torino, Italy</addr-line></nlm:aff></affiliation></author></analytic><series><title level="j">Immunology</title><idno type="ISSN">0019-2805</idno><idno type="eISSN">1365-2567</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>T cells are key players in immune action against the invasion of target cells expressing non-self antigens. During an immune response, antigen-specific T cells dynamically sculpt the antigenic distribution of target cells, and target cells concurrently shape the host’s repertoire of antigen-specific T cells. The succession of these reciprocal selective sweeps can result in ‘chase-and-escape’ dynamics and lead to immune evasion. It has been proposed that immune evasion can be countered by immunotherapy strategies aimed at regulating the three phases of the immune response orchestrated by antigen-specific T cells: expansion, contraction and memory. Here, we test this hypothesis with a mathematical model that considers the immune response as a selection contest between T cells and target cells. The outcomes of our model suggest that shortening the duration of the contraction phase and stabilizing as many T cells as possible inside the long-lived memory reservoir, using dual immunotherapies based on the cytokines interleukin-7 and/or interleukin-15 in combination with molecular factors that can keep the immunomodulatory action of these interleukins under control, should be an important focus of future immunotherapy research.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Immunology</journal-id><journal-id journal-id-type="iso-abbrev">Immunology</journal-id><journal-id journal-id-type="publisher-id">imm</journal-id><journal-title-group><journal-title>Immunology</journal-title></journal-title-group><issn pub-type="ppub">0019-2805</issn><issn pub-type="epub">1365-2567</issn><publisher><publisher-name>John Wiley & Sons, Ltd</publisher-name><publisher-loc>Chichester, UK</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26119966</article-id><article-id pub-id-type="pmc">4582968</article-id><article-id pub-id-type="doi">10.1111/imm.12500</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Articles</subject></subj-group></article-categories><title-group><article-title>Mathematical model reveals how regulating the three phases of T-cell response could counteract immune evasion</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Lorenzi</surname><given-names>Tommaso</given-names></name><xref ref-type="aff" rid="au1">1</xref><xref ref-type="author-notes" rid="fn1">†</xref><xref ref-type="corresp" rid="cor1"></xref></contrib><contrib contrib-type="author"><name><surname>Chisholm</surname><given-names>Rebecca H</given-names></name><xref ref-type="aff" rid="au2">2</xref><xref ref-type="author-notes" rid="fn1">†</xref></contrib><contrib contrib-type="author"><name><surname>Melensi</surname><given-names>Matteo</given-names></name><xref ref-type="aff" rid="au3">3</xref></contrib><contrib contrib-type="author"><name><surname>Lorz</surname><given-names>Alexander</given-names></name><xref ref-type="aff" rid="au4">4</xref><xref ref-type="aff" rid="au5">5</xref><xref ref-type="aff" rid="au6">6</xref></contrib><contrib contrib-type="author"><name><surname>Delitala</surname><given-names>Marcello</given-names></name><xref ref-type="aff" rid="au7">7</xref></contrib><aff id="au1"><label>1</label><institution>Centre de Mathématiques et de Leurs Applications, ENS Cachan, CNRS</institution><addr-line>Cachan Cedex, France</addr-line></aff><aff id="au2"><label>2</label><institution>School of Biotechnology and Biomolecular Sciences, University of New South Wales</institution><addr-line>Sydney, Australia</addr-line></aff><aff id="au3"><label>3</label><institution>Department of Health Sciences, A. Avogadro Università del Piemonte Orientale</institution><addr-line>Novara, Italy</addr-line></aff><aff id="au4"><label>4</label><institution>MAMBA Team, INRIA-Paris-Rocquencourt</institution><addr-line>Le Chesnay Cedex, France</addr-line></aff><aff id="au5"><label>5</label><institution>Laboratoire Jacques-Louis Lions, Sorbonne Universités, UPMC Univ Paris 06, UMR 7598</institution><addr-line>Paris, France</addr-line></aff><aff id="au6"><label>6</label><institution>Laboratoire Jacques-Louis Lions, CNRS, UMR 7598</institution><addr-line>Paris, France</addr-line></aff><aff id="au7"><label>7</label><institution>Department of Mathematical Sciences, Politecnico di Torino</institution><addr-line>Torino, Italy</addr-line></aff></contrib-group><author-notes><corresp id="cor1">Correspondence: Tommaso Lorenzi, Centre de Mathématiques et de Leurs Applications, École Normale Supérieure de Cachan, 61, Avenue du President Wilson, 94235 Cachan Cedex, France. Email: <email>lorenzi@cmla.ens-cachan.fr</email>, Senior author: Marcello Delitala
</corresp><fn id="fn1"><label>†</label><p>These primary authors contributed equally to this article.</p></fn></author-notes><pub-date pub-type="ppub"><month>10</month><year>2015</year></pub-date><pub-date pub-type="epub"><day>02</day><month>8</month><year>2015</year></pub-date><volume>146</volume><issue>2</issue><fpage>271</fpage><lpage>280</lpage><history><date date-type="received"><day>26</day><month>3</month><year>2015</year></date><date date-type="rev-recd"><day>21</day><month>6</month><year>2015</year></date><date date-type="accepted"><day>22</day><month>6</month><year>2015</year></date></history><permissions><copyright-statement>© 2015 John Wiley & Sons Ltd</copyright-statement><copyright-year>2015</copyright-year></permissions><abstract><p>T cells are key players in immune action against the invasion of target cells expressing non-self antigens. During an immune response, antigen-specific T cells dynamically sculpt the antigenic distribution of target cells, and target cells concurrently shape the host’s repertoire of antigen-specific T cells. The succession of these reciprocal selective sweeps can result in ‘chase-and-escape’ dynamics and lead to immune evasion. It has been proposed that immune evasion can be countered by immunotherapy strategies aimed at regulating the three phases of the immune response orchestrated by antigen-specific T cells: expansion, contraction and memory. Here, we test this hypothesis with a mathematical model that considers the immune response as a selection contest between T cells and target cells. The outcomes of our model suggest that shortening the duration of the contraction phase and stabilizing as many T cells as possible inside the long-lived memory reservoir, using dual immunotherapies based on the cytokines interleukin-7 and/or interleukin-15 in combination with molecular factors that can keep the immunomodulatory action of these interleukins under control, should be an important focus of future immunotherapy research.</p></abstract><kwd-group><kwd>mathematical modelling</kwd><kwd>memory</kwd><kwd>T cells</kwd><kwd>theoretical immunology</kwd><kwd>vaccination</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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