Cysteine Cathepsins in Tumor-Associated Immune Cells
Identifieur interne : 000969 ( Pmc/Curation ); précédent : 000968; suivant : 000970Cysteine Cathepsins in Tumor-Associated Immune Cells
Auteurs : Tanja Jakoš [Slovénie] ; Anja Pišlar [Slovénie] ; Anahid Jewett [États-Unis] ; Janko Kos [Slovénie]Source :
- Frontiers in Immunology [ 1664-3224 ] ; 2019.
Abstract
Cysteine cathepsins are key regulators of the innate and adaptive arms of the immune system. Their expression, activity, and subcellular localization are associated with the distinct development and differentiation stages of immune cells. They promote the activation of innate myeloid immune cells since they contribute to toll-like receptor signaling and to cytokine secretion. Furthermore, they control lysosomal biogenesis and autophagic flux, thus affecting innate immune cell survival and polarization. They also regulate bidirectional communication between the cell exterior and the cytoskeleton, thus influencing cell interactions, morphology, and motility. Importantly, cysteine cathepsins contribute to the priming of adaptive immune cells by controlling antigen presentation and are involved in cytotoxic granule mediated killing in cytotoxic T lymphocytes and natural killer cells. Cathepins'aberrant activity can be prevented by their endogenous inhibitors, cystatins. However, dysregulated proteolysis contributes significantly to tumor progression also by modulation of the antitumor immune response. Especially tumor-associated myeloid cells, such as tumor-associated macrophages and myeloid-derived suppressor cells, which are known for their tumor promoting and immunosuppressive functions, constitute the major source of excessive cysteine cathepsin activity in cancer. Since they are enriched in the tumor microenvironment, cysteine cathepsins represent exciting targets for development of new diagnostic and therapeutic moieties.
Url:
DOI: 10.3389/fimmu.2019.02037
PubMed: 31555270
PubMed Central: 6724555
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<front><div type="abstract" xml:lang="en"><p>Cysteine cathepsins are key regulators of the innate and adaptive arms of the immune system. Their expression, activity, and subcellular localization are associated with the distinct development and differentiation stages of immune cells. They promote the activation of innate myeloid immune cells since they contribute to toll-like receptor signaling and to cytokine secretion. Furthermore, they control lysosomal biogenesis and autophagic flux, thus affecting innate immune cell survival and polarization. They also regulate bidirectional communication between the cell exterior and the cytoskeleton, thus influencing cell interactions, morphology, and motility. Importantly, cysteine cathepsins contribute to the priming of adaptive immune cells by controlling antigen presentation and are involved in cytotoxic granule mediated killing in cytotoxic T lymphocytes and natural killer cells. Cathepins'aberrant activity can be prevented by their endogenous inhibitors, cystatins. However, dysregulated proteolysis contributes significantly to tumor progression also by modulation of the antitumor immune response. Especially tumor-associated myeloid cells, such as tumor-associated macrophages and myeloid-derived suppressor cells, which are known for their tumor promoting and immunosuppressive functions, constitute the major source of excessive cysteine cathepsin activity in cancer. Since they are enriched in the tumor microenvironment, cysteine cathepsins represent exciting targets for development of new diagnostic and therapeutic moieties.</p>
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<pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Front Immunol</journal-id>
<journal-id journal-id-type="iso-abbrev">Front Immunol</journal-id>
<journal-id journal-id-type="publisher-id">Front. Immunol.</journal-id>
<journal-title-group><journal-title>Frontiers in Immunology</journal-title>
</journal-title-group>
<issn pub-type="epub">1664-3224</issn>
<publisher><publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">31555270</article-id>
<article-id pub-id-type="pmc">6724555</article-id>
<article-id pub-id-type="doi">10.3389/fimmu.2019.02037</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Immunology</subject>
<subj-group><subject>Review</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group><article-title>Cysteine Cathepsins in Tumor-Associated Immune Cells</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Jakoš</surname>
<given-names>Tanja</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/748044/overview"></uri>
</contrib>
<contrib contrib-type="author"><name><surname>Pišlar</surname>
<given-names>Anja</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/498587/overview"></uri>
</contrib>
<contrib contrib-type="author"><name><surname>Jewett</surname>
<given-names>Anahid</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
<uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/116826/overview"></uri>
</contrib>
<contrib contrib-type="author"><name><surname>Kos</surname>
<given-names>Janko</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
<xref ref-type="corresp" rid="c001"><sup>*</sup>
</xref>
<uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/122213/overview"></uri>
</contrib>
</contrib-group>
<aff id="aff1"><sup>1</sup>
<institution>Faculty of Pharmacy, University of Ljubljana</institution>
,<addr-line>Ljubljana</addr-line>
,<country>Slovenia</country>
</aff>
<aff id="aff2"><sup>2</sup>
<institution>UCLA School of Dentistry and Medicine</institution>
,<addr-line>Los Angeles, CA</addr-line>
,<country>United States</country>
</aff>
<aff id="aff3"><sup>3</sup>
<institution>Department of Biotechnology, Jožef Stefan Institute</institution>
,<addr-line>Ljubljana</addr-line>
,<country>Slovenia</country>
</aff>
<author-notes><fn fn-type="edited-by"><p>Edited by: Khashayarsha Khazaie, Mayo Clinic College of Medicine and Science, United States</p>
</fn>
<fn fn-type="edited-by"><p>Reviewed by: Elias Gounaris, Northwestern University, United States; Julian Pardo, Fundacion Agencia Aragonesa para la Investigacion y el Desarrollo, Spain; Milica M. Perisic Nanut, Jožef Stefan Institute (IJS), Slovenia</p>
</fn>
<corresp id="c001">*Correspondence: Janko Kos <email>janko.kos@ffa.uni-lj.si</email>
</corresp>
<fn fn-type="other" id="fn001"><p>This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Immunology</p>
</fn>
</author-notes>
<pub-date pub-type="epub"><day>28</day>
<month>8</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="collection"><year>2019</year>
</pub-date>
<volume>10</volume>
<elocation-id>2037</elocation-id>
<history><date date-type="received"><day>31</day>
<month>5</month>
<year>2019</year>
</date>
<date date-type="accepted"><day>12</day>
<month>8</month>
<year>2019</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2019 Jakoš, Pišlar, Jewett and Kos.</copyright-statement>
<copyright-year>2019</copyright-year>
<copyright-holder>Jakoš, Pišlar, Jewett and Kos</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p>
</license>
</permissions>
<abstract><p>Cysteine cathepsins are key regulators of the innate and adaptive arms of the immune system. Their expression, activity, and subcellular localization are associated with the distinct development and differentiation stages of immune cells. They promote the activation of innate myeloid immune cells since they contribute to toll-like receptor signaling and to cytokine secretion. Furthermore, they control lysosomal biogenesis and autophagic flux, thus affecting innate immune cell survival and polarization. They also regulate bidirectional communication between the cell exterior and the cytoskeleton, thus influencing cell interactions, morphology, and motility. Importantly, cysteine cathepsins contribute to the priming of adaptive immune cells by controlling antigen presentation and are involved in cytotoxic granule mediated killing in cytotoxic T lymphocytes and natural killer cells. Cathepins'aberrant activity can be prevented by their endogenous inhibitors, cystatins. However, dysregulated proteolysis contributes significantly to tumor progression also by modulation of the antitumor immune response. Especially tumor-associated myeloid cells, such as tumor-associated macrophages and myeloid-derived suppressor cells, which are known for their tumor promoting and immunosuppressive functions, constitute the major source of excessive cysteine cathepsin activity in cancer. Since they are enriched in the tumor microenvironment, cysteine cathepsins represent exciting targets for development of new diagnostic and therapeutic moieties.</p>
</abstract>
<kwd-group><kwd>cysteine cathepsins</kwd>
<kwd>cystatins</kwd>
<kwd>immune response</kwd>
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