Listeria monocytogenes (Lm)-LLO immunotherapies reduce the immunosuppressive activity of myeloid-derived suppressor cells and regulatory T cells in the tumor microenvironment
Myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg) are major components of the immune suppressive cells that potentially limit the effectiveness of an immunotherapy-based treatment. Both of these suppressive cell types have been shown to expand in tumor models and promote T-cell d...
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| Veröffentlicht in: | Journal of immunotherapy (1997) 2013-11, Vol.36 (9), p.468-476 |
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| container_end_page | 476 |
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| container_title | Journal of immunotherapy (1997) |
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| creator | Wallecha, Anu Singh, Reshma Malinina, Inga |
| description | Myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg) are major components of the immune suppressive cells that potentially limit the effectiveness of an immunotherapy-based treatment. Both of these suppressive cell types have been shown to expand in tumor models and promote T-cell dysfunction that in turn favors tumor progression. This study demonstrates that Listeria monocytogenes (Lm)-LLO immunotherapies effect on the suppressive ability of MDSC and Treg in the tumor microenvironment (TME), resulting in a loss in the ability of these cells to suppress T cells. This alteration of immunosuppression in the TME was an inherent property of all Lm-LLO immunotherapies tested and was independent of the tumor model. The virtually total loss in the suppressive ability of these cells in the TME was linked to the reduction in the expression of arginase I in MDSC and IL-10 in Treg. The results presented here provide insight into a novel mechanism of Lm-LLO immunotherapies that potentially contributes to therapeutic antitumor responses. |
| doi_str_mv | 10.1097/CJI.0000000000000000 |
| format | Article |
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Both of these suppressive cell types have been shown to expand in tumor models and promote T-cell dysfunction that in turn favors tumor progression. This study demonstrates that Listeria monocytogenes (Lm)-LLO immunotherapies effect on the suppressive ability of MDSC and Treg in the tumor microenvironment (TME), resulting in a loss in the ability of these cells to suppress T cells. This alteration of immunosuppression in the TME was an inherent property of all Lm-LLO immunotherapies tested and was independent of the tumor model. The virtually total loss in the suppressive ability of these cells in the TME was linked to the reduction in the expression of arginase I in MDSC and IL-10 in Treg. 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Both of these suppressive cell types have been shown to expand in tumor models and promote T-cell dysfunction that in turn favors tumor progression. This study demonstrates that Listeria monocytogenes (Lm)-LLO immunotherapies effect on the suppressive ability of MDSC and Treg in the tumor microenvironment (TME), resulting in a loss in the ability of these cells to suppress T cells. This alteration of immunosuppression in the TME was an inherent property of all Lm-LLO immunotherapies tested and was independent of the tumor model. The virtually total loss in the suppressive ability of these cells in the TME was linked to the reduction in the expression of arginase I in MDSC and IL-10 in Treg. The results presented here provide insight into a novel mechanism of Lm-LLO immunotherapies that potentially contributes to therapeutic antitumor responses.</description><subject>Animals</subject><subject>Arginase - genetics</subject><subject>Arginase - immunology</subject><subject>Arginase - metabolism</subject><subject>Bacterial Toxins - immunology</subject><subject>Cancer Vaccines - immunology</subject><subject>Cancer Vaccines - therapeutic use</subject><subject>Cell Line, Tumor</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Gene Expression - immunology</subject><subject>Heat-Shock Proteins - immunology</subject><subject>Hemolysin Proteins - immunology</subject><subject>Immune Tolerance - immunology</subject><subject>Immunotherapy - methods</subject><subject>Interleukin-10 - genetics</subject><subject>Interleukin-10 - immunology</subject><subject>Interleukin-10 - metabolism</subject><subject>Listeria monocytogenes</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Myeloid Cells - immunology</subject><subject>Myeloid Cells - metabolism</subject><subject>Neoplasms, Experimental - genetics</subject><subject>Neoplasms, Experimental - metabolism</subject><subject>Neoplasms, Experimental - therapy</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>T-Lymphocytes, Regulatory - metabolism</subject><subject>Tumor Microenvironment - drug effects</subject><subject>Tumor Microenvironment - genetics</subject><subject>Tumor Microenvironment - immunology</subject><issn>1524-9557</issn><issn>1537-4513</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1u1TAQhSNERX_gDRDysixS_Bs7S3RFaVGkbso6cpxxMYrjYDtXykvxjPVtb1l0gze2znxzZqxTVR8JviK4lV92P26v8KvzpjojgsmaC8LeHt6U160Q8rQ6T-k3xrShnL6rTiknXDChzqq_nUsZotPIhzmYLYcHmCGhy85_rrvuDjnv1znkXxD14kohwrgaQEU4ltK6LBFScntA2mS3d3lDwSK_wRTcWI_FfQ8jeuFCRAamKSE9j8XtYZ10DnFD90fZzU_mefWF9M7EAPPexTB7mPP76sTqKcGH431R_bz-dr-7qbu777e7r11tOJO5BqOZZFhKKklrVcOYaKjFAzXaUs0bq8ZmIEZZBWpUljVc20FpbVtjjWQDu6gun32XGP6skHLvXTrsp2cIa-qJaDChVCrxf5RzzlpOW1VQ_oyWT6UUwfZLdF7HrSe4P4Tal1D716GWtk_HCevgYfzX9JIiewRQz6Iv</recordid><startdate>20131101</startdate><enddate>20131101</enddate><creator>Wallecha, Anu</creator><creator>Singh, Reshma</creator><creator>Malinina, Inga</creator><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><scope>7QL</scope><scope>7T5</scope><scope>C1K</scope><scope>H94</scope></search><sort><creationdate>20131101</creationdate><title>Listeria monocytogenes (Lm)-LLO immunotherapies reduce the immunosuppressive activity of myeloid-derived suppressor cells and regulatory T cells in the tumor microenvironment</title><author>Wallecha, Anu ; Singh, Reshma ; Malinina, Inga</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c437t-eca3730772719f8633562f0b2caf2a46f8d6b1c8f8e8d8f364afb8aaf9cfc73b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Arginase - genetics</topic><topic>Arginase - immunology</topic><topic>Arginase - metabolism</topic><topic>Bacterial Toxins - immunology</topic><topic>Cancer Vaccines - immunology</topic><topic>Cancer Vaccines - therapeutic use</topic><topic>Cell Line, Tumor</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Gene Expression - immunology</topic><topic>Heat-Shock Proteins - immunology</topic><topic>Hemolysin Proteins - immunology</topic><topic>Immune Tolerance - immunology</topic><topic>Immunotherapy - methods</topic><topic>Interleukin-10 - genetics</topic><topic>Interleukin-10 - immunology</topic><topic>Interleukin-10 - metabolism</topic><topic>Listeria monocytogenes</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C57BL</topic><topic>Myeloid Cells - immunology</topic><topic>Myeloid Cells - metabolism</topic><topic>Neoplasms, Experimental - genetics</topic><topic>Neoplasms, Experimental - metabolism</topic><topic>Neoplasms, Experimental - therapy</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>T-Lymphocytes, Regulatory - metabolism</topic><topic>Tumor Microenvironment - drug effects</topic><topic>Tumor Microenvironment - genetics</topic><topic>Tumor Microenvironment - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wallecha, Anu</creatorcontrib><creatorcontrib>Singh, Reshma</creatorcontrib><creatorcontrib>Malinina, Inga</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><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Journal of immunotherapy (1997)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wallecha, Anu</au><au>Singh, Reshma</au><au>Malinina, Inga</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Listeria monocytogenes (Lm)-LLO immunotherapies reduce the immunosuppressive activity of myeloid-derived suppressor cells and regulatory T cells in the tumor microenvironment</atitle><jtitle>Journal of immunotherapy (1997)</jtitle><addtitle>J Immunother</addtitle><date>2013-11-01</date><risdate>2013</risdate><volume>36</volume><issue>9</issue><spage>468</spage><epage>476</epage><pages>468-476</pages><issn>1524-9557</issn><eissn>1537-4513</eissn><abstract>Myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg) are major components of the immune suppressive cells that potentially limit the effectiveness of an immunotherapy-based treatment. Both of these suppressive cell types have been shown to expand in tumor models and promote T-cell dysfunction that in turn favors tumor progression. This study demonstrates that Listeria monocytogenes (Lm)-LLO immunotherapies effect on the suppressive ability of MDSC and Treg in the tumor microenvironment (TME), resulting in a loss in the ability of these cells to suppress T cells. This alteration of immunosuppression in the TME was an inherent property of all Lm-LLO immunotherapies tested and was independent of the tumor model. The virtually total loss in the suppressive ability of these cells in the TME was linked to the reduction in the expression of arginase I in MDSC and IL-10 in Treg. 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| subjects | Animals Arginase - genetics Arginase - immunology Arginase - metabolism Bacterial Toxins - immunology Cancer Vaccines - immunology Cancer Vaccines - therapeutic use Cell Line, Tumor Female Flow Cytometry Gene Expression - immunology Heat-Shock Proteins - immunology Hemolysin Proteins - immunology Immune Tolerance - immunology Immunotherapy - methods Interleukin-10 - genetics Interleukin-10 - immunology Interleukin-10 - metabolism Listeria monocytogenes Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Myeloid Cells - immunology Myeloid Cells - metabolism Neoplasms, Experimental - genetics Neoplasms, Experimental - metabolism Neoplasms, Experimental - therapy Reverse Transcriptase Polymerase Chain Reaction T-Lymphocytes, Regulatory - immunology T-Lymphocytes, Regulatory - metabolism Tumor Microenvironment - drug effects Tumor Microenvironment - genetics Tumor Microenvironment - immunology |
| title | Listeria monocytogenes (Lm)-LLO immunotherapies reduce the immunosuppressive activity of myeloid-derived suppressor cells and regulatory T cells in the tumor microenvironment |
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