Immunotherapy of cancer via mediation of cytotoxic T lymphocytes by methionine enkephalin (MENK)
Abstract The aim of this study was to investigate the immunological mechanisms by which synthetic methionine enkephalin (MENK) exerts therapeutic effects on tumor growth. Our findings in vivo or in vitro show that MENK treatment either in vivo or in vitro could up-regulate the percentages of CD8+T c...
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| Veröffentlicht in: | Cancer letters 2014-03, Vol.344 (2), p.212-222 |
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| container_title | Cancer letters |
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| creator | Li, Weiwei Chen, Wenna Herberman, Ronald B Plotnikoff, Nicolas P Youkilis, Gene Griffin, Noreen Wang, Enhua Lu, Changlong Shan, Fengping |
| description | Abstract The aim of this study was to investigate the immunological mechanisms by which synthetic methionine enkephalin (MENK) exerts therapeutic effects on tumor growth. Our findings in vivo or in vitro show that MENK treatment either in vivo or in vitro could up-regulate the percentages of CD8+T cells, induce markers of activated T cells, increased cytotoxic activity against mouse S180 tumor cells and increase secretion of IFNγ. In addition, the adoptively transferred CD8+T cells, after either in vitro or in vivo treatment with MENK, result in significantly increased survival of S180 tumor-bearing mice and significant shrinkage in tumor growth. Opioid receptors are detected on normal CD8+T cells and exposure to MENK leads to increased expression of opioid receptors. Interaction between MENK and the opioid receptors on CD8+T cells appears to be essential for the activation of CTL, since the addition of naltrexone (NTX), an opioid receptor antagonist, significantly inhibits all of the effects of MENK. The evidence obtained indicates that the MENK-induced T cell signaling is associated with a significant up-regulation of Ca2+ influx into the cytoplasm and the translocation of NFAT2 into nucleus, and these signaling effects are also inhibited by naltrexone. |
| doi_str_mv | 10.1016/j.canlet.2013.10.029 |
| format | Article |
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Our findings in vivo or in vitro show that MENK treatment either in vivo or in vitro could up-regulate the percentages of CD8+T cells, induce markers of activated T cells, increased cytotoxic activity against mouse S180 tumor cells and increase secretion of IFNγ. In addition, the adoptively transferred CD8+T cells, after either in vitro or in vivo treatment with MENK, result in significantly increased survival of S180 tumor-bearing mice and significant shrinkage in tumor growth. Opioid receptors are detected on normal CD8+T cells and exposure to MENK leads to increased expression of opioid receptors. Interaction between MENK and the opioid receptors on CD8+T cells appears to be essential for the activation of CTL, since the addition of naltrexone (NTX), an opioid receptor antagonist, significantly inhibits all of the effects of MENK. The evidence obtained indicates that the MENK-induced T cell signaling is associated with a significant up-regulation of Ca2+ influx into the cytoplasm and the translocation of NFAT2 into nucleus, and these signaling effects are also inhibited by naltrexone.</description><identifier>ISSN: 0304-3835</identifier><identifier>EISSN: 1872-7980</identifier><identifier>DOI: 10.1016/j.canlet.2013.10.029</identifier><identifier>PMID: 24291668</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>Animals ; Antitumor ; Apoptosis ; Calcium - metabolism ; CD8+T cells ; CD8-Positive T-Lymphocytes - drug effects ; CD8-Positive T-Lymphocytes - immunology ; Cell growth ; Cell Nucleus - immunology ; Cell Nucleus - metabolism ; Cytotoxicity ; Enkephalin, Methionine - immunology ; Enkephalin, Methionine - pharmacology ; Flow cytometry ; Hematology, Oncology and Palliative Medicine ; Hypotheses ; Immune system ; Immunotherapy, Adoptive - methods ; Laboratory animals ; Lymphocyte Activation - drug effects ; Lymphocytes ; Male ; Methionine enkephalin ; Mice ; Mice, Inbred C57BL ; Opioid receptors ; Random Allocation ; Receptors, Opioid, delta - biosynthesis ; Receptors, Opioid, delta - immunology ; Receptors, Opioid, mu - biosynthesis ; Receptors, Opioid, mu - immunology ; Sarcoma 180 - drug therapy ; Sarcoma 180 - immunology ; Sarcoma 180 - therapy ; Studies ; T-Lymphocytes, Cytotoxic - drug effects ; T-Lymphocytes, Cytotoxic - immunology ; Tumors ; Viral infections</subject><ispartof>Cancer letters, 2014-03, Vol.344 (2), p.212-222</ispartof><rights>Elsevier Ireland Ltd</rights><rights>2013 Elsevier Ireland Ltd</rights><rights>Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.</rights><rights>Copyright Elsevier Limited Mar 28, 2014</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-462d3b85dddc815f0b779362824b50bee86714470a052fb3fc31da3c943e5f003</citedby><cites>FETCH-LOGICAL-c478t-462d3b85dddc815f0b779362824b50bee86714470a052fb3fc31da3c943e5f003</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0304383513007842$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27902,27903,65308</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24291668$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Weiwei</creatorcontrib><creatorcontrib>Chen, Wenna</creatorcontrib><creatorcontrib>Herberman, Ronald B</creatorcontrib><creatorcontrib>Plotnikoff, Nicolas P</creatorcontrib><creatorcontrib>Youkilis, Gene</creatorcontrib><creatorcontrib>Griffin, Noreen</creatorcontrib><creatorcontrib>Wang, Enhua</creatorcontrib><creatorcontrib>Lu, Changlong</creatorcontrib><creatorcontrib>Shan, Fengping</creatorcontrib><title>Immunotherapy of cancer via mediation of cytotoxic T lymphocytes by methionine enkephalin (MENK)</title><title>Cancer letters</title><addtitle>Cancer Lett</addtitle><description>Abstract The aim of this study was to investigate the immunological mechanisms by which synthetic methionine enkephalin (MENK) exerts therapeutic effects on tumor growth. Our findings in vivo or in vitro show that MENK treatment either in vivo or in vitro could up-regulate the percentages of CD8+T cells, induce markers of activated T cells, increased cytotoxic activity against mouse S180 tumor cells and increase secretion of IFNγ. In addition, the adoptively transferred CD8+T cells, after either in vitro or in vivo treatment with MENK, result in significantly increased survival of S180 tumor-bearing mice and significant shrinkage in tumor growth. Opioid receptors are detected on normal CD8+T cells and exposure to MENK leads to increased expression of opioid receptors. Interaction between MENK and the opioid receptors on CD8+T cells appears to be essential for the activation of CTL, since the addition of naltrexone (NTX), an opioid receptor antagonist, significantly inhibits all of the effects of MENK. The evidence obtained indicates that the MENK-induced T cell signaling is associated with a significant up-regulation of Ca2+ influx into the cytoplasm and the translocation of NFAT2 into nucleus, and these signaling effects are also inhibited by naltrexone.</description><subject>Animals</subject><subject>Antitumor</subject><subject>Apoptosis</subject><subject>Calcium - metabolism</subject><subject>CD8+T cells</subject><subject>CD8-Positive T-Lymphocytes - drug effects</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cell growth</subject><subject>Cell Nucleus - immunology</subject><subject>Cell Nucleus - metabolism</subject><subject>Cytotoxicity</subject><subject>Enkephalin, Methionine - immunology</subject><subject>Enkephalin, Methionine - pharmacology</subject><subject>Flow cytometry</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Hypotheses</subject><subject>Immune system</subject><subject>Immunotherapy, Adoptive - methods</subject><subject>Laboratory animals</subject><subject>Lymphocyte Activation - drug effects</subject><subject>Lymphocytes</subject><subject>Male</subject><subject>Methionine enkephalin</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Opioid receptors</subject><subject>Random Allocation</subject><subject>Receptors, Opioid, delta - biosynthesis</subject><subject>Receptors, Opioid, delta - immunology</subject><subject>Receptors, Opioid, mu - biosynthesis</subject><subject>Receptors, Opioid, mu - immunology</subject><subject>Sarcoma 180 - drug therapy</subject><subject>Sarcoma 180 - immunology</subject><subject>Sarcoma 180 - therapy</subject><subject>Studies</subject><subject>T-Lymphocytes, Cytotoxic - drug effects</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>Tumors</subject><subject>Viral infections</subject><issn>0304-3835</issn><issn>1872-7980</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk1v1DAQhi0EokvhHyAUiUt7yDL-ip0LEqpaqChwoJyN40y03iZxGicV-fc4bAGpl54sjZ55rZlnCHlNYUuBFu_2W2f7FqctA8pTaQusfEI2VCuWq1LDU7IBDiLnmssj8iLGPQBIoeRzcsQEK2lR6A35edl1cx-mHY52WLLQZCnV4ZjdeZt1WHs7-dD_qS9TmMIv77LrrF26YRdSBWNWLYmbdonyPWbY3-Cws63vs5Mv518_n74kzxrbRnx1_x6THxfn12ef8qtvHy_PPlzlTig95aJgNa-0rOvaaSobqJQqecE0E5WEClEXigqhwIJkTcUbx2ltuSsFx0QDPyYnh9xhDLczxsl0PjpsW9tjmKOhkgEvuJT8cVSkVJBKlwl9-wDdh3ns0yApUKqC0QJkosSBcmOIccTGDKPv7LgYCmaVZfbmIMusstZqkpXa3tyHz1Va9b-mv3YS8P4AYFrcncfRROcx6an9iG4ydfCP_fAwwCUz3tn2BheM_2cxkRkw39eDWe-FcgClBeO_ATULuok</recordid><startdate>20140328</startdate><enddate>20140328</enddate><creator>Li, Weiwei</creator><creator>Chen, Wenna</creator><creator>Herberman, Ronald B</creator><creator>Plotnikoff, Nicolas P</creator><creator>Youkilis, Gene</creator><creator>Griffin, Noreen</creator><creator>Wang, Enhua</creator><creator>Lu, Changlong</creator><creator>Shan, Fengping</creator><general>Elsevier Ireland Ltd</general><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>7T5</scope></search><sort><creationdate>20140328</creationdate><title>Immunotherapy of cancer via mediation of cytotoxic T lymphocytes by methionine enkephalin (MENK)</title><author>Li, Weiwei ; Chen, Wenna ; Herberman, Ronald B ; Plotnikoff, Nicolas P ; Youkilis, Gene ; Griffin, Noreen ; Wang, Enhua ; Lu, Changlong ; Shan, Fengping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c478t-462d3b85dddc815f0b779362824b50bee86714470a052fb3fc31da3c943e5f003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Antitumor</topic><topic>Apoptosis</topic><topic>Calcium - metabolism</topic><topic>CD8+T cells</topic><topic>CD8-Positive T-Lymphocytes - drug effects</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Cell growth</topic><topic>Cell Nucleus - immunology</topic><topic>Cell Nucleus - metabolism</topic><topic>Cytotoxicity</topic><topic>Enkephalin, Methionine - immunology</topic><topic>Enkephalin, Methionine - pharmacology</topic><topic>Flow cytometry</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Hypotheses</topic><topic>Immune system</topic><topic>Immunotherapy, Adoptive - methods</topic><topic>Laboratory animals</topic><topic>Lymphocyte Activation - drug effects</topic><topic>Lymphocytes</topic><topic>Male</topic><topic>Methionine enkephalin</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Opioid receptors</topic><topic>Random Allocation</topic><topic>Receptors, Opioid, delta - biosynthesis</topic><topic>Receptors, Opioid, delta - immunology</topic><topic>Receptors, Opioid, mu - biosynthesis</topic><topic>Receptors, Opioid, mu - immunology</topic><topic>Sarcoma 180 - drug therapy</topic><topic>Sarcoma 180 - immunology</topic><topic>Sarcoma 180 - therapy</topic><topic>Studies</topic><topic>T-Lymphocytes, Cytotoxic - drug effects</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>Tumors</topic><topic>Viral infections</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Weiwei</creatorcontrib><creatorcontrib>Chen, Wenna</creatorcontrib><creatorcontrib>Herberman, Ronald B</creatorcontrib><creatorcontrib>Plotnikoff, Nicolas P</creatorcontrib><creatorcontrib>Youkilis, Gene</creatorcontrib><creatorcontrib>Griffin, Noreen</creatorcontrib><creatorcontrib>Wang, Enhua</creatorcontrib><creatorcontrib>Lu, Changlong</creatorcontrib><creatorcontrib>Shan, Fengping</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><jtitle>Cancer letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Weiwei</au><au>Chen, Wenna</au><au>Herberman, Ronald B</au><au>Plotnikoff, Nicolas P</au><au>Youkilis, Gene</au><au>Griffin, Noreen</au><au>Wang, Enhua</au><au>Lu, Changlong</au><au>Shan, Fengping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunotherapy of cancer via mediation of cytotoxic T lymphocytes by methionine enkephalin (MENK)</atitle><jtitle>Cancer letters</jtitle><addtitle>Cancer Lett</addtitle><date>2014-03-28</date><risdate>2014</risdate><volume>344</volume><issue>2</issue><spage>212</spage><epage>222</epage><pages>212-222</pages><issn>0304-3835</issn><eissn>1872-7980</eissn><abstract>Abstract The aim of this study was to investigate the immunological mechanisms by which synthetic methionine enkephalin (MENK) exerts therapeutic effects on tumor growth. Our findings in vivo or in vitro show that MENK treatment either in vivo or in vitro could up-regulate the percentages of CD8+T cells, induce markers of activated T cells, increased cytotoxic activity against mouse S180 tumor cells and increase secretion of IFNγ. In addition, the adoptively transferred CD8+T cells, after either in vitro or in vivo treatment with MENK, result in significantly increased survival of S180 tumor-bearing mice and significant shrinkage in tumor growth. Opioid receptors are detected on normal CD8+T cells and exposure to MENK leads to increased expression of opioid receptors. Interaction between MENK and the opioid receptors on CD8+T cells appears to be essential for the activation of CTL, since the addition of naltrexone (NTX), an opioid receptor antagonist, significantly inhibits all of the effects of MENK. The evidence obtained indicates that the MENK-induced T cell signaling is associated with a significant up-regulation of Ca2+ influx into the cytoplasm and the translocation of NFAT2 into nucleus, and these signaling effects are also inhibited by naltrexone.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>24291668</pmid><doi>10.1016/j.canlet.2013.10.029</doi><tpages>11</tpages></addata></record> |
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| ispartof | Cancer letters, 2014-03, Vol.344 (2), p.212-222 |
| issn | 0304-3835 1872-7980 |
| language | eng |
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| subjects | Animals Antitumor Apoptosis Calcium - metabolism CD8+T cells CD8-Positive T-Lymphocytes - drug effects CD8-Positive T-Lymphocytes - immunology Cell growth Cell Nucleus - immunology Cell Nucleus - metabolism Cytotoxicity Enkephalin, Methionine - immunology Enkephalin, Methionine - pharmacology Flow cytometry Hematology, Oncology and Palliative Medicine Hypotheses Immune system Immunotherapy, Adoptive - methods Laboratory animals Lymphocyte Activation - drug effects Lymphocytes Male Methionine enkephalin Mice Mice, Inbred C57BL Opioid receptors Random Allocation Receptors, Opioid, delta - biosynthesis Receptors, Opioid, delta - immunology Receptors, Opioid, mu - biosynthesis Receptors, Opioid, mu - immunology Sarcoma 180 - drug therapy Sarcoma 180 - immunology Sarcoma 180 - therapy Studies T-Lymphocytes, Cytotoxic - drug effects T-Lymphocytes, Cytotoxic - immunology Tumors Viral infections |
| title | Immunotherapy of cancer via mediation of cytotoxic T lymphocytes by methionine enkephalin (MENK) |
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