Leukemia blast-induced T-cell anergy demonstrated by leukemia-derived dendritic cells in acute myelogenous leukemia
To elucidate the mechanism of immunologic escape of leukemia cells and establish an effective anti-leukemia immunotherapy, we attempted to generate dendritic cells from leukemia cells in patients with acute myelogenous leukemia (AML). Using these leukemia-derived dendritic cells, we investigated leu...
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| Veröffentlicht in: | Experimental hematology 2001-06, Vol.29 (6), p.709-719 |
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| creator | Narita, Miwako Takahashi, Masuhiro Liu, Aichun Nikkuni, Kohji Furukawa, Tatsuo Toba, Ken Koyama, Satoru Takai, Kazue Sanada, Masayoshi Aizawa, Yoshifusa |
| description | To elucidate the mechanism of immunologic escape of leukemia cells and establish an effective anti-leukemia immunotherapy, we attempted to generate dendritic cells from leukemia cells in patients with acute myelogenous leukemia (AML). Using these leukemia-derived dendritic cells, we investigated leukemia cell-associated T-cell anergy.
Leukemia cells of 30 patients with AML were cultured with granulocyte-macrophage colony-stimulating factor, interleukin-4, and tumor necrosis factor-α. Cultured leukemia cells were evaluated for antigen-presenting ability by mixed leukocyte culture (MLC). Normal lymphocytes, which were cocultured with leukemia blasts in the first MLC, were cultured with leukemia-derived dendritic cells in the second MLC.
In cultures of leukemia cells from 21 of 30 patients examined, cells with stellate morphology and cell fractions with CD1a
+ and/or CD83
+ were present. Autologous MLC using lymphocytes obtained in remission phase as responders as well as allogeneic MLC demonstrated antigen-presenting ability in leukemia-derived dendritic cells. Leukemia cells of FAB-M0, M1, M2, M3, or M6 morphology/phenotype gave rise to dendritic cells as well as leukemia cells of M5. The leukemic origin of dendritic cells was suggested by in situ hybridization. By coculture with CD80
− leukemia blasts, the response of normal lymphocytes to leukemia-derived dendritic cells cultured from the same individual as that of leukemia blasts was markedly reduced, compared with the lymphocytes cultured with leukemia blasts from a different individual as leukemia blasts.
Escape of leukemia cells from anti-leukemia immunity may be associated with T-cell anergy caused by leukemia blasts. The results of the present study suggest that leukemia-derived dendritic cells can be applied efficiently in anti-leukemia immunotherapy. |
| doi_str_mv | 10.1016/S0301-472X(01)00636-1 |
| format | Article |
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Leukemia cells of 30 patients with AML were cultured with granulocyte-macrophage colony-stimulating factor, interleukin-4, and tumor necrosis factor-α. Cultured leukemia cells were evaluated for antigen-presenting ability by mixed leukocyte culture (MLC). Normal lymphocytes, which were cocultured with leukemia blasts in the first MLC, were cultured with leukemia-derived dendritic cells in the second MLC.
In cultures of leukemia cells from 21 of 30 patients examined, cells with stellate morphology and cell fractions with CD1a
+ and/or CD83
+ were present. Autologous MLC using lymphocytes obtained in remission phase as responders as well as allogeneic MLC demonstrated antigen-presenting ability in leukemia-derived dendritic cells. Leukemia cells of FAB-M0, M1, M2, M3, or M6 morphology/phenotype gave rise to dendritic cells as well as leukemia cells of M5. The leukemic origin of dendritic cells was suggested by in situ hybridization. By coculture with CD80
− leukemia blasts, the response of normal lymphocytes to leukemia-derived dendritic cells cultured from the same individual as that of leukemia blasts was markedly reduced, compared with the lymphocytes cultured with leukemia blasts from a different individual as leukemia blasts.
Escape of leukemia cells from anti-leukemia immunity may be associated with T-cell anergy caused by leukemia blasts. The results of the present study suggest that leukemia-derived dendritic cells can be applied efficiently in anti-leukemia immunotherapy.</description><identifier>ISSN: 0301-472X</identifier><identifier>EISSN: 1873-2399</identifier><identifier>DOI: 10.1016/S0301-472X(01)00636-1</identifier><identifier>PMID: 11378266</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Blast Crisis - immunology ; Clonal Anergy - immunology ; Coculture Techniques ; Colony-Stimulating Factors - pharmacology ; Dendritic Cells - drug effects ; Dendritic Cells - immunology ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology ; Humans ; Interleukin-4 - pharmacology ; Karyotyping ; Leukemia, Myeloid, Acute - blood ; Leukemia, Myeloid, Acute - genetics ; Leukemia, Myeloid, Acute - immunology ; Leukemia, Myeloid, Acute - pathology ; Leukocyte Count ; Lymphocyte Culture Test, Mixed ; Male ; Middle Aged ; T-Lymphocytes - immunology ; Tumor Cells, Cultured ; Tumor Necrosis Factor-alpha - pharmacology</subject><ispartof>Experimental hematology, 2001-06, Vol.29 (6), p.709-719</ispartof><rights>2001 International Society for Experimental Hematology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c408t-92f9c6895f2cc614d961645b8ae07942af6c4f4d75b272ebc5ebd1594a719cf93</citedby><cites>FETCH-LOGICAL-c408t-92f9c6895f2cc614d961645b8ae07942af6c4f4d75b272ebc5ebd1594a719cf93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0301-472X(01)00636-1$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11378266$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Narita, Miwako</creatorcontrib><creatorcontrib>Takahashi, Masuhiro</creatorcontrib><creatorcontrib>Liu, Aichun</creatorcontrib><creatorcontrib>Nikkuni, Kohji</creatorcontrib><creatorcontrib>Furukawa, Tatsuo</creatorcontrib><creatorcontrib>Toba, Ken</creatorcontrib><creatorcontrib>Koyama, Satoru</creatorcontrib><creatorcontrib>Takai, Kazue</creatorcontrib><creatorcontrib>Sanada, Masayoshi</creatorcontrib><creatorcontrib>Aizawa, Yoshifusa</creatorcontrib><title>Leukemia blast-induced T-cell anergy demonstrated by leukemia-derived dendritic cells in acute myelogenous leukemia</title><title>Experimental hematology</title><addtitle>Exp Hematol</addtitle><description>To elucidate the mechanism of immunologic escape of leukemia cells and establish an effective anti-leukemia immunotherapy, we attempted to generate dendritic cells from leukemia cells in patients with acute myelogenous leukemia (AML). Using these leukemia-derived dendritic cells, we investigated leukemia cell-associated T-cell anergy.
Leukemia cells of 30 patients with AML were cultured with granulocyte-macrophage colony-stimulating factor, interleukin-4, and tumor necrosis factor-α. Cultured leukemia cells were evaluated for antigen-presenting ability by mixed leukocyte culture (MLC). Normal lymphocytes, which were cocultured with leukemia blasts in the first MLC, were cultured with leukemia-derived dendritic cells in the second MLC.
In cultures of leukemia cells from 21 of 30 patients examined, cells with stellate morphology and cell fractions with CD1a
+ and/or CD83
+ were present. Autologous MLC using lymphocytes obtained in remission phase as responders as well as allogeneic MLC demonstrated antigen-presenting ability in leukemia-derived dendritic cells. Leukemia cells of FAB-M0, M1, M2, M3, or M6 morphology/phenotype gave rise to dendritic cells as well as leukemia cells of M5. The leukemic origin of dendritic cells was suggested by in situ hybridization. By coculture with CD80
− leukemia blasts, the response of normal lymphocytes to leukemia-derived dendritic cells cultured from the same individual as that of leukemia blasts was markedly reduced, compared with the lymphocytes cultured with leukemia blasts from a different individual as leukemia blasts.
Escape of leukemia cells from anti-leukemia immunity may be associated with T-cell anergy caused by leukemia blasts. The results of the present study suggest that leukemia-derived dendritic cells can be applied efficiently in anti-leukemia immunotherapy.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Blast Crisis - immunology</subject><subject>Clonal Anergy - immunology</subject><subject>Coculture Techniques</subject><subject>Colony-Stimulating Factors - pharmacology</subject><subject>Dendritic Cells - drug effects</subject><subject>Dendritic Cells - immunology</subject><subject>Female</subject><subject>Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology</subject><subject>Humans</subject><subject>Interleukin-4 - pharmacology</subject><subject>Karyotyping</subject><subject>Leukemia, Myeloid, Acute - blood</subject><subject>Leukemia, Myeloid, Acute - genetics</subject><subject>Leukemia, Myeloid, Acute - immunology</subject><subject>Leukemia, Myeloid, Acute - pathology</subject><subject>Leukocyte Count</subject><subject>Lymphocyte Culture Test, Mixed</subject><subject>Male</subject><subject>Middle Aged</subject><subject>T-Lymphocytes - immunology</subject><subject>Tumor Cells, Cultured</subject><subject>Tumor Necrosis Factor-alpha - pharmacology</subject><issn>0301-472X</issn><issn>1873-2399</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1r3DAQhkVJaTZJf0KLTiE9qBnZsmSdQghpWljIIRvoTcjSeFHrj0SyA_vvo_1ge-xpYPS8mpmHkC8cvnPg8voJSuBMqOL3FfBvALKUjH8gC16rkhWl1idkcUROyVlKfwCgqjR8Iqecl6oupFyQtMT5L_bB0qazaWJh8LNDT1fMYddRO2Bcb6jHfhzSFO2Un5oN7Q4h5jGGt9zzOPgYpuDoNpZoGKh184S032A3rnEY53RMXZCPre0Sfj7Uc_L8435195MtHx9-3d0umRNQT0wXrXay1lVbOCe58FpyKaqmtghKi8K20olWeFU1hSqwcRU2nldaWMW1a3V5Ti73_77E8XXGNJk-pO1--aq8j1GgQSgOGaz2oItjShFb8xJDb-PGcDBb22Zn22xVmlx3tg3Pua-HAXPTo_-XOujNwM0ewHzmW8Bokgs4ZMEhopuMH8N_RrwD-D-RZA</recordid><startdate>20010601</startdate><enddate>20010601</enddate><creator>Narita, Miwako</creator><creator>Takahashi, Masuhiro</creator><creator>Liu, Aichun</creator><creator>Nikkuni, Kohji</creator><creator>Furukawa, Tatsuo</creator><creator>Toba, Ken</creator><creator>Koyama, Satoru</creator><creator>Takai, Kazue</creator><creator>Sanada, Masayoshi</creator><creator>Aizawa, Yoshifusa</creator><general>Elsevier Inc</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>7X8</scope></search><sort><creationdate>20010601</creationdate><title>Leukemia blast-induced T-cell anergy demonstrated by leukemia-derived dendritic cells in acute myelogenous leukemia</title><author>Narita, Miwako ; Takahashi, Masuhiro ; Liu, Aichun ; Nikkuni, Kohji ; Furukawa, Tatsuo ; Toba, Ken ; Koyama, Satoru ; Takai, Kazue ; Sanada, Masayoshi ; Aizawa, Yoshifusa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c408t-92f9c6895f2cc614d961645b8ae07942af6c4f4d75b272ebc5ebd1594a719cf93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Blast Crisis - immunology</topic><topic>Clonal Anergy - immunology</topic><topic>Coculture Techniques</topic><topic>Colony-Stimulating Factors - pharmacology</topic><topic>Dendritic Cells - drug effects</topic><topic>Dendritic Cells - immunology</topic><topic>Female</topic><topic>Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology</topic><topic>Humans</topic><topic>Interleukin-4 - pharmacology</topic><topic>Karyotyping</topic><topic>Leukemia, Myeloid, Acute - blood</topic><topic>Leukemia, Myeloid, Acute - genetics</topic><topic>Leukemia, Myeloid, Acute - immunology</topic><topic>Leukemia, Myeloid, Acute - pathology</topic><topic>Leukocyte Count</topic><topic>Lymphocyte Culture Test, Mixed</topic><topic>Male</topic><topic>Middle Aged</topic><topic>T-Lymphocytes - immunology</topic><topic>Tumor Cells, Cultured</topic><topic>Tumor Necrosis Factor-alpha - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Narita, Miwako</creatorcontrib><creatorcontrib>Takahashi, Masuhiro</creatorcontrib><creatorcontrib>Liu, Aichun</creatorcontrib><creatorcontrib>Nikkuni, Kohji</creatorcontrib><creatorcontrib>Furukawa, Tatsuo</creatorcontrib><creatorcontrib>Toba, Ken</creatorcontrib><creatorcontrib>Koyama, Satoru</creatorcontrib><creatorcontrib>Takai, Kazue</creatorcontrib><creatorcontrib>Sanada, Masayoshi</creatorcontrib><creatorcontrib>Aizawa, Yoshifusa</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental hematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Narita, Miwako</au><au>Takahashi, Masuhiro</au><au>Liu, Aichun</au><au>Nikkuni, Kohji</au><au>Furukawa, Tatsuo</au><au>Toba, Ken</au><au>Koyama, Satoru</au><au>Takai, Kazue</au><au>Sanada, Masayoshi</au><au>Aizawa, Yoshifusa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Leukemia blast-induced T-cell anergy demonstrated by leukemia-derived dendritic cells in acute myelogenous leukemia</atitle><jtitle>Experimental hematology</jtitle><addtitle>Exp Hematol</addtitle><date>2001-06-01</date><risdate>2001</risdate><volume>29</volume><issue>6</issue><spage>709</spage><epage>719</epage><pages>709-719</pages><issn>0301-472X</issn><eissn>1873-2399</eissn><abstract>To elucidate the mechanism of immunologic escape of leukemia cells and establish an effective anti-leukemia immunotherapy, we attempted to generate dendritic cells from leukemia cells in patients with acute myelogenous leukemia (AML). Using these leukemia-derived dendritic cells, we investigated leukemia cell-associated T-cell anergy.
Leukemia cells of 30 patients with AML were cultured with granulocyte-macrophage colony-stimulating factor, interleukin-4, and tumor necrosis factor-α. Cultured leukemia cells were evaluated for antigen-presenting ability by mixed leukocyte culture (MLC). Normal lymphocytes, which were cocultured with leukemia blasts in the first MLC, were cultured with leukemia-derived dendritic cells in the second MLC.
In cultures of leukemia cells from 21 of 30 patients examined, cells with stellate morphology and cell fractions with CD1a
+ and/or CD83
+ were present. Autologous MLC using lymphocytes obtained in remission phase as responders as well as allogeneic MLC demonstrated antigen-presenting ability in leukemia-derived dendritic cells. Leukemia cells of FAB-M0, M1, M2, M3, or M6 morphology/phenotype gave rise to dendritic cells as well as leukemia cells of M5. The leukemic origin of dendritic cells was suggested by in situ hybridization. By coculture with CD80
− leukemia blasts, the response of normal lymphocytes to leukemia-derived dendritic cells cultured from the same individual as that of leukemia blasts was markedly reduced, compared with the lymphocytes cultured with leukemia blasts from a different individual as leukemia blasts.
Escape of leukemia cells from anti-leukemia immunity may be associated with T-cell anergy caused by leukemia blasts. The results of the present study suggest that leukemia-derived dendritic cells can be applied efficiently in anti-leukemia immunotherapy.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>11378266</pmid><doi>10.1016/S0301-472X(01)00636-1</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Aged Aged, 80 and over Blast Crisis - immunology Clonal Anergy - immunology Coculture Techniques Colony-Stimulating Factors - pharmacology Dendritic Cells - drug effects Dendritic Cells - immunology Female Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology Humans Interleukin-4 - pharmacology Karyotyping Leukemia, Myeloid, Acute - blood Leukemia, Myeloid, Acute - genetics Leukemia, Myeloid, Acute - immunology Leukemia, Myeloid, Acute - pathology Leukocyte Count Lymphocyte Culture Test, Mixed Male Middle Aged T-Lymphocytes - immunology Tumor Cells, Cultured Tumor Necrosis Factor-alpha - pharmacology |
| title | Leukemia blast-induced T-cell anergy demonstrated by leukemia-derived dendritic cells in acute myelogenous leukemia |
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