Modulation of antitumor immunity contributes to the enhanced therapeutic efficacy of liposomal oxaliplatin in mouse model
Immune modulation of the tumor microenvironment has been reported to participate in the therapeutic efficacy of many chemotherapeutic agents. Recently, we reported that liposomal encapsulation of oxaliplatin (l‐OHP) within PEGylated liposomes conferred a superior antitumor efficacy to free l‐OHP in...
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| Veröffentlicht in: | Cancer science 2017-09, Vol.108 (9), p.1864-1869 |
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| creator | Shimizu, Taro Abu Lila, Amr S. Nishio, Miho Doi, Yusuke Ando, Hidenori Ukawa, Masami Ishima, Yu Ishida, Tatsuhiro |
| description | Immune modulation of the tumor microenvironment has been reported to participate in the therapeutic efficacy of many chemotherapeutic agents. Recently, we reported that liposomal encapsulation of oxaliplatin (l‐OHP) within PEGylated liposomes conferred a superior antitumor efficacy to free l‐OHP in murine colorectal carcinoma‐bearing mice through permitting preferential accumulation of the encapsulated drug within tumor tissue. However, the contribution of the immune‐modulatory properties of liposomal l‐OHP and/or free l‐OHP to the overall antitumor efficacy was not elucidated. In the present study, therefore, we investigated the effect of liposomal encapsulation of l‐OHP within PEGylated liposomes on the antitumor immunity in both immunocompetent and immunodeficient mice. Liposomal l‐OHP significantly suppressed the growth of tumors implanted in immunocompetent mice, but not in immunodeficient mice. In immunocompetent mice, liposomal l‐OHP increased the tumor MHC‐1 level and preserved antitumor immunity through decreasing the number of immune suppressor cells, including regulatory T cells, myeloid‐derived suppressor cells, and tumor‐associated macrophages, which collectively suppress CD8+ T cell‐mediated tumor cells killing. In contrast, free l‐OHP ruined antitumor immunity. These results suggest that the antitumor efficacy of liposomal l‐OHP is attributed, on the one hand, to its immunomodulatory effect on tumor immune microenvironment that is superior to that of free l‐OHP, and on the other hand, to its direct cytotoxic effect on tumor cells.
The antitumor efficacy of liposomal l‐OHP is attributed, on the one hand, to its immunomodulatory effect on tumor immune microenvironment that is superior to that of free l‐OHP, and on the other hand, to its direct cytotoxic effect on tumor cells. |
| doi_str_mv | 10.1111/cas.13305 |
| format | Article |
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The antitumor efficacy of liposomal l‐OHP is attributed, on the one hand, to its immunomodulatory effect on tumor immune microenvironment that is superior to that of free l‐OHP, and on the other hand, to its direct cytotoxic effect on tumor cells.</description><identifier>ISSN: 1347-9032</identifier><identifier>EISSN: 1349-7006</identifier><identifier>DOI: 10.1111/cas.13305</identifier><identifier>PMID: 28643902</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Animals ; Antineoplastic Agents - administration & dosage ; Antitumor activity ; Antitumor immunity ; Cancer therapies ; CD8 antigen ; Cell Line, Tumor ; Chemotherapy ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - drug therapy ; Colorectal Neoplasms - immunology ; Cytotoxicity ; drug delivery system ; Drug dosages ; Drug Screening Assays, Antitumor ; Encapsulation ; Histocompatibility Antigens Class I - metabolism ; Immunity ; Immunodeficiency ; Immunologic Factors - administration & dosage ; Immunomodulation ; Immunoregulation ; Immunotherapy ; liposome ; Liposomes ; Lymphocytes ; Lymphocytes T ; Macrophages ; Major histocompatibility complex ; Male ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Organoplatinum Compounds - administration & dosage ; Original ; Oxaliplatin ; Peptides ; Polyethylene glycol ; Studies ; Suppressor cells ; Tumor cells ; Tumors</subject><ispartof>Cancer science, 2017-09, Vol.108 (9), p.1864-1869</ispartof><rights>2017 The Authors. published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>2017. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5775-54f0416f0b14a6b1257a439eef800fb4018844c8d7640255929759dddf8d32c13</citedby><cites>FETCH-LOGICAL-c5775-54f0416f0b14a6b1257a439eef800fb4018844c8d7640255929759dddf8d32c13</cites><orcidid>0000-0002-1333-6465</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5581521/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5581521/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,11542,27903,27904,45553,45554,46031,46455,53770,53772</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28643902$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shimizu, Taro</creatorcontrib><creatorcontrib>Abu Lila, Amr S.</creatorcontrib><creatorcontrib>Nishio, Miho</creatorcontrib><creatorcontrib>Doi, Yusuke</creatorcontrib><creatorcontrib>Ando, Hidenori</creatorcontrib><creatorcontrib>Ukawa, Masami</creatorcontrib><creatorcontrib>Ishima, Yu</creatorcontrib><creatorcontrib>Ishida, Tatsuhiro</creatorcontrib><title>Modulation of antitumor immunity contributes to the enhanced therapeutic efficacy of liposomal oxaliplatin in mouse model</title><title>Cancer science</title><addtitle>Cancer Sci</addtitle><description>Immune modulation of the tumor microenvironment has been reported to participate in the therapeutic efficacy of many chemotherapeutic agents. Recently, we reported that liposomal encapsulation of oxaliplatin (l‐OHP) within PEGylated liposomes conferred a superior antitumor efficacy to free l‐OHP in murine colorectal carcinoma‐bearing mice through permitting preferential accumulation of the encapsulated drug within tumor tissue. However, the contribution of the immune‐modulatory properties of liposomal l‐OHP and/or free l‐OHP to the overall antitumor efficacy was not elucidated. In the present study, therefore, we investigated the effect of liposomal encapsulation of l‐OHP within PEGylated liposomes on the antitumor immunity in both immunocompetent and immunodeficient mice. Liposomal l‐OHP significantly suppressed the growth of tumors implanted in immunocompetent mice, but not in immunodeficient mice. In immunocompetent mice, liposomal l‐OHP increased the tumor MHC‐1 level and preserved antitumor immunity through decreasing the number of immune suppressor cells, including regulatory T cells, myeloid‐derived suppressor cells, and tumor‐associated macrophages, which collectively suppress CD8+ T cell‐mediated tumor cells killing. In contrast, free l‐OHP ruined antitumor immunity. These results suggest that the antitumor efficacy of liposomal l‐OHP is attributed, on the one hand, to its immunomodulatory effect on tumor immune microenvironment that is superior to that of free l‐OHP, and on the other hand, to its direct cytotoxic effect on tumor cells.
The antitumor efficacy of liposomal l‐OHP is attributed, on the one hand, to its immunomodulatory effect on tumor immune microenvironment that is superior to that of free l‐OHP, and on the other hand, to its direct cytotoxic effect on tumor cells.</description><subject>Animals</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antitumor activity</subject><subject>Antitumor immunity</subject><subject>Cancer therapies</subject><subject>CD8 antigen</subject><subject>Cell Line, Tumor</subject><subject>Chemotherapy</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - drug therapy</subject><subject>Colorectal Neoplasms - immunology</subject><subject>Cytotoxicity</subject><subject>drug delivery system</subject><subject>Drug dosages</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Encapsulation</subject><subject>Histocompatibility Antigens Class I - metabolism</subject><subject>Immunity</subject><subject>Immunodeficiency</subject><subject>Immunologic Factors - administration & dosage</subject><subject>Immunomodulation</subject><subject>Immunoregulation</subject><subject>Immunotherapy</subject><subject>liposome</subject><subject>Liposomes</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Macrophages</subject><subject>Major histocompatibility complex</subject><subject>Male</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Neoplasm Transplantation</subject><subject>Organoplatinum Compounds - administration & dosage</subject><subject>Original</subject><subject>Oxaliplatin</subject><subject>Peptides</subject><subject>Polyethylene glycol</subject><subject>Studies</subject><subject>Suppressor cells</subject><subject>Tumor cells</subject><subject>Tumors</subject><issn>1347-9032</issn><issn>1349-7006</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kU1vFSEUhonR2C8X_gFD4qqLaYGBGWbTpLmxrUmNC-2aMHx4aWbglg91_r1Mb9voQkI4nPDkPS95AXiP0Rmu61zJdIbbFrFX4BC3dGh6hLrXj_e-GVBLDsBRSvcItR0d6FtwQHhH2wGRQ7B8CbpMMrvgYbBQ-uxymUOEbp6Ld3mBKvgc3ViySTAHmLcGGr-VXhm9NlHuTMlOQWOtU1Itq8zkdiGFWU4w_Ja1WQd4WPccSjL11GY6AW-snJJ591SPwd3Vp--bm-b26_XnzeVto1jfs4ZRiyjuLBoxld2ICetl9W6M5QjZkSLMOaWK676jiDA2kKFng9bact0ShdtjcLHX3ZVxNlqZ-h05iV10s4yLCNKJf1-824of4adgjGNGVoGPTwIxPBSTsrgPJfrqWRDCOe_wgFGlTveUiiGlaOzLBIzEmpKoKYnHlCr74W9LL-RzLBU43wO_3GSW_yuJzeW3veQfkCCeow</recordid><startdate>201709</startdate><enddate>201709</enddate><creator>Shimizu, Taro</creator><creator>Abu Lila, Amr S.</creator><creator>Nishio, Miho</creator><creator>Doi, Yusuke</creator><creator>Ando, Hidenori</creator><creator>Ukawa, Masami</creator><creator>Ishima, Yu</creator><creator>Ishida, Tatsuhiro</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><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>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1333-6465</orcidid></search><sort><creationdate>201709</creationdate><title>Modulation of antitumor immunity contributes to the enhanced therapeutic efficacy of liposomal oxaliplatin in mouse model</title><author>Shimizu, Taro ; 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Recently, we reported that liposomal encapsulation of oxaliplatin (l‐OHP) within PEGylated liposomes conferred a superior antitumor efficacy to free l‐OHP in murine colorectal carcinoma‐bearing mice through permitting preferential accumulation of the encapsulated drug within tumor tissue. However, the contribution of the immune‐modulatory properties of liposomal l‐OHP and/or free l‐OHP to the overall antitumor efficacy was not elucidated. In the present study, therefore, we investigated the effect of liposomal encapsulation of l‐OHP within PEGylated liposomes on the antitumor immunity in both immunocompetent and immunodeficient mice. Liposomal l‐OHP significantly suppressed the growth of tumors implanted in immunocompetent mice, but not in immunodeficient mice. In immunocompetent mice, liposomal l‐OHP increased the tumor MHC‐1 level and preserved antitumor immunity through decreasing the number of immune suppressor cells, including regulatory T cells, myeloid‐derived suppressor cells, and tumor‐associated macrophages, which collectively suppress CD8+ T cell‐mediated tumor cells killing. In contrast, free l‐OHP ruined antitumor immunity. These results suggest that the antitumor efficacy of liposomal l‐OHP is attributed, on the one hand, to its immunomodulatory effect on tumor immune microenvironment that is superior to that of free l‐OHP, and on the other hand, to its direct cytotoxic effect on tumor cells.
The antitumor efficacy of liposomal l‐OHP is attributed, on the one hand, to its immunomodulatory effect on tumor immune microenvironment that is superior to that of free l‐OHP, and on the other hand, to its direct cytotoxic effect on tumor cells.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>28643902</pmid><doi>10.1111/cas.13305</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-1333-6465</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antineoplastic Agents - administration & dosage Antitumor activity Antitumor immunity Cancer therapies CD8 antigen Cell Line, Tumor Chemotherapy Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - drug therapy Colorectal Neoplasms - immunology Cytotoxicity drug delivery system Drug dosages Drug Screening Assays, Antitumor Encapsulation Histocompatibility Antigens Class I - metabolism Immunity Immunodeficiency Immunologic Factors - administration & dosage Immunomodulation Immunoregulation Immunotherapy liposome Liposomes Lymphocytes Lymphocytes T Macrophages Major histocompatibility complex Male Mice, Inbred BALB C Mice, Nude Neoplasm Transplantation Organoplatinum Compounds - administration & dosage Original Oxaliplatin Peptides Polyethylene glycol Studies Suppressor cells Tumor cells Tumors |
| title | Modulation of antitumor immunity contributes to the enhanced therapeutic efficacy of liposomal oxaliplatin in mouse model |
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