Specifically differentiated T cell subset promotes tumor immunity over fatal immunity
Allogeneic immune cells, particularly T cells in donor grafts, recognize and eliminate leukemic cells via graft-versus-leukemia (GVL) reactivity, and transfer of these cells is often used for high-risk hematological malignancies, including acute myeloid leukemia. Unfortunately, these cells also atta...
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| Veröffentlicht in: | The Journal of experimental medicine 2017-12, Vol.214 (12), p.3577-3596 |
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| creator | Ramadan, Abdulraouf Griesenauer, Brad Adom, Djamilatou Kapur, Reuben Hanenberg, Helmut Liu, Chen Kaplan, Mark H Paczesny, Sophie |
| description | Allogeneic immune cells, particularly T cells in donor grafts, recognize and eliminate leukemic cells via graft-versus-leukemia (GVL) reactivity, and transfer of these cells is often used for high-risk hematological malignancies, including acute myeloid leukemia. Unfortunately, these cells also attack host normal tissues through the often fatal graft-versus-host disease (GVHD). Full separation of GVL activity from GVHD has yet to be achieved. Here, we show that, in mice and humans, a population of interleukin-9 (IL-9)-producing T cells activated via the ST2-IL-33 pathway (T9
cells) increases GVL while decreasing GVHD through two opposing mechanisms: protection from fatal immunity by amphiregulin expression and augmentation of antileukemic activity compared with T9, T1, and unmanipulated T cells through CD8α expression. Thus, adoptive transfer of allogeneic T9
cells offers an attractive approach for separating GVL activity from GVHD. |
| doi_str_mv | 10.1084/jem.20170041 |
| format | Article |
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cells) increases GVL while decreasing GVHD through two opposing mechanisms: protection from fatal immunity by amphiregulin expression and augmentation of antileukemic activity compared with T9, T1, and unmanipulated T cells through CD8α expression. Thus, adoptive transfer of allogeneic T9
cells offers an attractive approach for separating GVL activity from GVHD.</description><identifier>ISSN: 0022-1007</identifier><identifier>ISSN: 1540-9538</identifier><identifier>EISSN: 1540-9538</identifier><identifier>DOI: 10.1084/jem.20170041</identifier><identifier>PMID: 29038366</identifier><language>eng</language><publisher>United States: Rockefeller University Press</publisher><subject>Acute myeloid leukemia ; Adoptive Transfer ; Amphiregulin ; Amphiregulin - metabolism ; Animal tissues ; Animals ; Anticancer properties ; Augmentation ; CD8 antigen ; Cell Communication ; Cell Differentiation - immunology ; Cell Line ; Cell Line, Tumor ; Cytotoxicity, Immunologic ; Epithelial Cells - metabolism ; Graft vs Host Disease - pathology ; Graft-versus-host reaction ; Grafting ; Grafts ; Hematology ; Humans ; Immune system ; Immunity ; Immunologic Memory ; Immunological memory ; Interleukin 9 ; Interleukin-1 Receptor-Like 1 Protein - metabolism ; Interleukin-33 - metabolism ; Interleukin-9 - metabolism ; Interleukins ; Intestines - pathology ; Leukemia ; Leukemia - immunology ; Leukemia - pathology ; Lymphocytes ; Lymphocytes T ; Mice, Inbred BALB C ; Myeloid leukemia ; Phenotype ; Proto-Oncogene Proteins - metabolism ; Signal Transduction ; Survival Analysis ; T cell receptors ; T-Lymphocyte Subsets - cytology ; T-Lymphocyte Subsets - immunology ; Trans-Activators - metabolism</subject><ispartof>The Journal of experimental medicine, 2017-12, Vol.214 (12), p.3577-3596</ispartof><rights>2017 Ramadan et al.</rights><rights>Copyright Rockefeller University Press Dec 4, 2017</rights><rights>2017 Ramadan et al. 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-6704cbce79a015def68efa735e34c10924ae886e7930f500e421b700f7c6747c3</citedby><cites>FETCH-LOGICAL-c412t-6704cbce79a015def68efa735e34c10924ae886e7930f500e421b700f7c6747c3</cites><orcidid>0000-0002-2923-8245 ; 0000-0001-5571-2775 ; 0000-0003-4128-0996</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29038366$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ramadan, Abdulraouf</creatorcontrib><creatorcontrib>Griesenauer, Brad</creatorcontrib><creatorcontrib>Adom, Djamilatou</creatorcontrib><creatorcontrib>Kapur, Reuben</creatorcontrib><creatorcontrib>Hanenberg, Helmut</creatorcontrib><creatorcontrib>Liu, Chen</creatorcontrib><creatorcontrib>Kaplan, Mark H</creatorcontrib><creatorcontrib>Paczesny, Sophie</creatorcontrib><title>Specifically differentiated T cell subset promotes tumor immunity over fatal immunity</title><title>The Journal of experimental medicine</title><addtitle>J Exp Med</addtitle><description>Allogeneic immune cells, particularly T cells in donor grafts, recognize and eliminate leukemic cells via graft-versus-leukemia (GVL) reactivity, and transfer of these cells is often used for high-risk hematological malignancies, including acute myeloid leukemia. Unfortunately, these cells also attack host normal tissues through the often fatal graft-versus-host disease (GVHD). Full separation of GVL activity from GVHD has yet to be achieved. Here, we show that, in mice and humans, a population of interleukin-9 (IL-9)-producing T cells activated via the ST2-IL-33 pathway (T9
cells) increases GVL while decreasing GVHD through two opposing mechanisms: protection from fatal immunity by amphiregulin expression and augmentation of antileukemic activity compared with T9, T1, and unmanipulated T cells through CD8α expression. Thus, adoptive transfer of allogeneic T9
cells offers an attractive approach for separating GVL activity from GVHD.</description><subject>Acute myeloid leukemia</subject><subject>Adoptive Transfer</subject><subject>Amphiregulin</subject><subject>Amphiregulin - metabolism</subject><subject>Animal tissues</subject><subject>Animals</subject><subject>Anticancer properties</subject><subject>Augmentation</subject><subject>CD8 antigen</subject><subject>Cell Communication</subject><subject>Cell Differentiation - immunology</subject><subject>Cell Line</subject><subject>Cell Line, Tumor</subject><subject>Cytotoxicity, Immunologic</subject><subject>Epithelial Cells - metabolism</subject><subject>Graft vs Host Disease - pathology</subject><subject>Graft-versus-host reaction</subject><subject>Grafting</subject><subject>Grafts</subject><subject>Hematology</subject><subject>Humans</subject><subject>Immune system</subject><subject>Immunity</subject><subject>Immunologic Memory</subject><subject>Immunological memory</subject><subject>Interleukin 9</subject><subject>Interleukin-1 Receptor-Like 1 Protein - metabolism</subject><subject>Interleukin-33 - metabolism</subject><subject>Interleukin-9 - metabolism</subject><subject>Interleukins</subject><subject>Intestines - pathology</subject><subject>Leukemia</subject><subject>Leukemia - immunology</subject><subject>Leukemia - pathology</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Mice, Inbred BALB C</subject><subject>Myeloid leukemia</subject><subject>Phenotype</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Signal Transduction</subject><subject>Survival Analysis</subject><subject>T cell receptors</subject><subject>T-Lymphocyte Subsets - cytology</subject><subject>T-Lymphocyte Subsets - immunology</subject><subject>Trans-Activators - metabolism</subject><issn>0022-1007</issn><issn>1540-9538</issn><issn>1540-9538</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc1LHTEUxUOp6PNj13UJdNOFozdfk5mNIKJVELqorkNe3k2bx8zkmWSE9983oj5aVxfu-XE4h0PIFwZnDDp5vsbxjAPTAJJ9IgumJDS9Et1nsgDgvGEA-oAc5rwGYFKqdp8c8B5EJ9p2QR5_bdAFH5wdhi1dBe8x4VSCLbiiD9ThMNA8LzMWuklxjAUzLfMYEw3jOE-hbGl8xkS9LXbY_Y7JnrdDxpO3e0Qeb64frm6b-58_7q4u7xsnGS9Nq0G6pUPdW2Bqhb7t0FstFArpGPRcWuy6tuoCvAJAydmyFvXatVpqJ47IxavvZl6OuHI1ebKD2aQw2rQ10QbzvzKFP-Z3fDZKsxYErwbf3wxSfJoxFzOG_FLaThjnbFivOAPeC1nRbx_QdZzTVOtVqquAEhIqdfpKuRRzTuh3YRiYl71M3cu871Xxr_8W2MHvA4m_JAqR9A</recordid><startdate>20171204</startdate><enddate>20171204</enddate><creator>Ramadan, Abdulraouf</creator><creator>Griesenauer, Brad</creator><creator>Adom, Djamilatou</creator><creator>Kapur, Reuben</creator><creator>Hanenberg, Helmut</creator><creator>Liu, Chen</creator><creator>Kaplan, Mark H</creator><creator>Paczesny, Sophie</creator><general>Rockefeller University Press</general><general>The Rockefeller University Press</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>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2923-8245</orcidid><orcidid>https://orcid.org/0000-0001-5571-2775</orcidid><orcidid>https://orcid.org/0000-0003-4128-0996</orcidid></search><sort><creationdate>20171204</creationdate><title>Specifically differentiated T cell subset promotes tumor immunity over fatal immunity</title><author>Ramadan, Abdulraouf ; 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Unfortunately, these cells also attack host normal tissues through the often fatal graft-versus-host disease (GVHD). Full separation of GVL activity from GVHD has yet to be achieved. Here, we show that, in mice and humans, a population of interleukin-9 (IL-9)-producing T cells activated via the ST2-IL-33 pathway (T9
cells) increases GVL while decreasing GVHD through two opposing mechanisms: protection from fatal immunity by amphiregulin expression and augmentation of antileukemic activity compared with T9, T1, and unmanipulated T cells through CD8α expression. Thus, adoptive transfer of allogeneic T9
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| subjects | Acute myeloid leukemia Adoptive Transfer Amphiregulin Amphiregulin - metabolism Animal tissues Animals Anticancer properties Augmentation CD8 antigen Cell Communication Cell Differentiation - immunology Cell Line Cell Line, Tumor Cytotoxicity, Immunologic Epithelial Cells - metabolism Graft vs Host Disease - pathology Graft-versus-host reaction Grafting Grafts Hematology Humans Immune system Immunity Immunologic Memory Immunological memory Interleukin 9 Interleukin-1 Receptor-Like 1 Protein - metabolism Interleukin-33 - metabolism Interleukin-9 - metabolism Interleukins Intestines - pathology Leukemia Leukemia - immunology Leukemia - pathology Lymphocytes Lymphocytes T Mice, Inbred BALB C Myeloid leukemia Phenotype Proto-Oncogene Proteins - metabolism Signal Transduction Survival Analysis T cell receptors T-Lymphocyte Subsets - cytology T-Lymphocyte Subsets - immunology Trans-Activators - metabolism |
| title | Specifically differentiated T cell subset promotes tumor immunity over fatal immunity |
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