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Targeting the immune microenvironment for ovarian cancer therapy
Ovarian cancer (OC) is an aggressive malignancy characterized by a complex immunosuppressive tumor microenvironment (TME). Immune checkpoint inhibitors have emerged as a breakthrough in cancer therapy by reactivating the antitumor immune response suppressed by tumor cells. However, in the case of OC...
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Published in: | Frontiers in immunology 2023-12, Vol.14, p.1328651-1328651 |
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description | Ovarian cancer (OC) is an aggressive malignancy characterized by a complex immunosuppressive tumor microenvironment (TME). Immune checkpoint inhibitors have emerged as a breakthrough in cancer therapy by reactivating the antitumor immune response suppressed by tumor cells. However, in the case of OC, these inhibitors have failed to demonstrate significant improvements in patient outcomes, and existing biomarkers have not yet identified promising subgroups. Consequently, there remains a pressing need to understand the interplay between OC tumor cells and their surrounding microenvironment to develop effective immunotherapeutic approaches. This review aims to provide an overview of the OC TME and explore its potential as a therapeutic strategy. Tumor-infiltrating lymphocytes (TILs) are major actors in OC TME. Evidence has been accumulating regarding the spontaneous TILS response against OC antigens. Activated T-helpers secrete a wide range of inflammatory cytokines with a supportive action on cytotoxic T-cells. Simultaneously, mature B-cells are recruited and play a significant antitumor role through opsonization of target antigens and T-cell recruitment. Macrophages also form an important subset of innate immunity (M1-macrophages) while participating in the immune-stimulation context. Finally, OC has shown to engage a significant natural-killer-cells immune response, exerting direct cytotoxicity without prior sensitization. Despite this initial cytotoxicity, OC cells develop various strategies to induce an immune-tolerant state. To this end, multiple immunosuppressive molecules are secreted to impair cytotoxic cells, recruit regulatory cells, alter antigen presentation, and effectively evade immune response. Consequently, OC TME is predominantly infiltrated by immunosuppressive cells such as FOXP3
regulatory T-cells, M2-polarized macrophages and myeloid-derived suppressor cells. Despite this strong immunosuppressive state, PD-1/PD-L1 inhibitors have failed to improve outcomes. Beyond PD-1/PD-L1, OC expresses multiple other immune checkpoints that contribute to immune evasion, and each representing potential immune targets. Novel immunotherapies are attempting to overcome the immunosuppressive state and induce specific immune responses using antibodies adoptive cell therapy or vaccines. Overall, the OC TME presents both opportunities and obstacles. Immunotherapeutic approaches continue to show promise, and next-generation inhibitors offer exciting opportunit |
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regulatory T-cells, M2-polarized macrophages and myeloid-derived suppressor cells. Despite this strong immunosuppressive state, PD-1/PD-L1 inhibitors have failed to improve outcomes. Beyond PD-1/PD-L1, OC expresses multiple other immune checkpoints that contribute to immune evasion, and each representing potential immune targets. Novel immunotherapies are attempting to overcome the immunosuppressive state and induce specific immune responses using antibodies adoptive cell therapy or vaccines. Overall, the OC TME presents both opportunities and obstacles. Immunotherapeutic approaches continue to show promise, and next-generation inhibitors offer exciting opportunities. However, tailoring therapies to individual immune characteristics will be critical for the success of these treatments.</description><identifier>ISSN: 1664-3224</identifier><identifier>EISSN: 1664-3224</identifier><identifier>DOI: 10.3389/fimmu.2023.1328651</identifier><identifier>PMID: 38164130</identifier><language>eng</language><publisher>Switzerland: Frontiers Media S.A</publisher><subject>adoptive cell therapy ; Female ; Humans ; immune microenvironment ; Immunology ; Immunosuppressive Agents - pharmacology ; Immunotherapy ; Lymphocytes, Tumor-Infiltrating ; ovarian cancer ; Ovarian Neoplasms - therapy ; Programmed Cell Death 1 Receptor ; T-Lymphocytes, Cytotoxic ; Tumor Microenvironment ; tumor-associated macrophages ; tumor-infiltrating lymphocytes</subject><ispartof>Frontiers in immunology, 2023-12, Vol.14, p.1328651-1328651</ispartof><rights>Copyright © 2023 Blanc-Durand, Clemence Wei Xian and Tan.</rights><rights>Copyright © 2023 Blanc-Durand, Clemence Wei Xian and Tan 2023 Blanc-Durand, Clemence Wei Xian and Tan</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c469t-e90492c4fbeb22fa65627a1df17611e1503cdda48eb2aad883491661176472193</citedby><cites>FETCH-LOGICAL-c469t-e90492c4fbeb22fa65627a1df17611e1503cdda48eb2aad883491661176472193</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10757966/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10757966/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38164130$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Blanc-Durand, Felix</creatorcontrib><creatorcontrib>Clemence Wei Xian, Lai</creatorcontrib><creatorcontrib>Tan, David S P</creatorcontrib><title>Targeting the immune microenvironment for ovarian cancer therapy</title><title>Frontiers in immunology</title><addtitle>Front Immunol</addtitle><description>Ovarian cancer (OC) is an aggressive malignancy characterized by a complex immunosuppressive tumor microenvironment (TME). Immune checkpoint inhibitors have emerged as a breakthrough in cancer therapy by reactivating the antitumor immune response suppressed by tumor cells. However, in the case of OC, these inhibitors have failed to demonstrate significant improvements in patient outcomes, and existing biomarkers have not yet identified promising subgroups. Consequently, there remains a pressing need to understand the interplay between OC tumor cells and their surrounding microenvironment to develop effective immunotherapeutic approaches. This review aims to provide an overview of the OC TME and explore its potential as a therapeutic strategy. Tumor-infiltrating lymphocytes (TILs) are major actors in OC TME. Evidence has been accumulating regarding the spontaneous TILS response against OC antigens. Activated T-helpers secrete a wide range of inflammatory cytokines with a supportive action on cytotoxic T-cells. Simultaneously, mature B-cells are recruited and play a significant antitumor role through opsonization of target antigens and T-cell recruitment. Macrophages also form an important subset of innate immunity (M1-macrophages) while participating in the immune-stimulation context. Finally, OC has shown to engage a significant natural-killer-cells immune response, exerting direct cytotoxicity without prior sensitization. Despite this initial cytotoxicity, OC cells develop various strategies to induce an immune-tolerant state. To this end, multiple immunosuppressive molecules are secreted to impair cytotoxic cells, recruit regulatory cells, alter antigen presentation, and effectively evade immune response. Consequently, OC TME is predominantly infiltrated by immunosuppressive cells such as FOXP3
regulatory T-cells, M2-polarized macrophages and myeloid-derived suppressor cells. Despite this strong immunosuppressive state, PD-1/PD-L1 inhibitors have failed to improve outcomes. Beyond PD-1/PD-L1, OC expresses multiple other immune checkpoints that contribute to immune evasion, and each representing potential immune targets. Novel immunotherapies are attempting to overcome the immunosuppressive state and induce specific immune responses using antibodies adoptive cell therapy or vaccines. Overall, the OC TME presents both opportunities and obstacles. Immunotherapeutic approaches continue to show promise, and next-generation inhibitors offer exciting opportunities. However, tailoring therapies to individual immune characteristics will be critical for the success of these treatments.</description><subject>adoptive cell therapy</subject><subject>Female</subject><subject>Humans</subject><subject>immune microenvironment</subject><subject>Immunology</subject><subject>Immunosuppressive Agents - pharmacology</subject><subject>Immunotherapy</subject><subject>Lymphocytes, Tumor-Infiltrating</subject><subject>ovarian cancer</subject><subject>Ovarian Neoplasms - therapy</subject><subject>Programmed Cell Death 1 Receptor</subject><subject>T-Lymphocytes, Cytotoxic</subject><subject>Tumor Microenvironment</subject><subject>tumor-associated macrophages</subject><subject>tumor-infiltrating lymphocytes</subject><issn>1664-3224</issn><issn>1664-3224</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNpVkU1P3DAQhi3UChDlD3BAOfayW4_tOPaprVA_kJB6oWdr4kwWo8TeOtmV-Pc47BaBLx75nXlmxi9jV8DXUhr7pQ_juFsLLuQapDC6hhN2DlqrlRRCfXgTn7HLaXrk5SgrpaxP2Zk0oBVIfs6-3WPe0BzippofqFqgkaox-Jwo7kNOcaQ4V33KVdpjDhgrj9FTXtIzbp8-sY89DhNdHu8L9vfnj_ub36u7P79ub77frbzSdl6RLd2FV31LrRA96lqLBqHrodEABDWXvutQmSIjdsZIZcsGUGTVCLDygt0euF3CR7fNYcT85BIG9_KQ8sZhnoMfyKlOmNbWGnsCVTfcgCqh15baxtiWF9bXA2u7a0fqfNkw4_AO-l6J4cFt0t4Bb-rGal0In4-EnP7taJrdGCZPw4CR0m5ywnLLjbXNMrg4pJYvnaZM_Wsf4G6x0r1Y6RYr3dHKUnT9dsLXkv_GyWeygptd</recordid><startdate>20231218</startdate><enddate>20231218</enddate><creator>Blanc-Durand, Felix</creator><creator>Clemence Wei Xian, Lai</creator><creator>Tan, David S P</creator><general>Frontiers Media S.A</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><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20231218</creationdate><title>Targeting the immune microenvironment for ovarian cancer therapy</title><author>Blanc-Durand, Felix ; Clemence Wei Xian, Lai ; Tan, David S P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c469t-e90492c4fbeb22fa65627a1df17611e1503cdda48eb2aad883491661176472193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>adoptive cell therapy</topic><topic>Female</topic><topic>Humans</topic><topic>immune microenvironment</topic><topic>Immunology</topic><topic>Immunosuppressive Agents - pharmacology</topic><topic>Immunotherapy</topic><topic>Lymphocytes, Tumor-Infiltrating</topic><topic>ovarian cancer</topic><topic>Ovarian Neoplasms - therapy</topic><topic>Programmed Cell Death 1 Receptor</topic><topic>T-Lymphocytes, Cytotoxic</topic><topic>Tumor Microenvironment</topic><topic>tumor-associated macrophages</topic><topic>tumor-infiltrating lymphocytes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Blanc-Durand, Felix</creatorcontrib><creatorcontrib>Clemence Wei Xian, Lai</creatorcontrib><creatorcontrib>Tan, David S P</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>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>Frontiers in immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Blanc-Durand, Felix</au><au>Clemence Wei Xian, Lai</au><au>Tan, David S P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Targeting the immune microenvironment for ovarian cancer therapy</atitle><jtitle>Frontiers in immunology</jtitle><addtitle>Front Immunol</addtitle><date>2023-12-18</date><risdate>2023</risdate><volume>14</volume><spage>1328651</spage><epage>1328651</epage><pages>1328651-1328651</pages><issn>1664-3224</issn><eissn>1664-3224</eissn><abstract>Ovarian cancer (OC) is an aggressive malignancy characterized by a complex immunosuppressive tumor microenvironment (TME). Immune checkpoint inhibitors have emerged as a breakthrough in cancer therapy by reactivating the antitumor immune response suppressed by tumor cells. However, in the case of OC, these inhibitors have failed to demonstrate significant improvements in patient outcomes, and existing biomarkers have not yet identified promising subgroups. Consequently, there remains a pressing need to understand the interplay between OC tumor cells and their surrounding microenvironment to develop effective immunotherapeutic approaches. This review aims to provide an overview of the OC TME and explore its potential as a therapeutic strategy. Tumor-infiltrating lymphocytes (TILs) are major actors in OC TME. Evidence has been accumulating regarding the spontaneous TILS response against OC antigens. Activated T-helpers secrete a wide range of inflammatory cytokines with a supportive action on cytotoxic T-cells. Simultaneously, mature B-cells are recruited and play a significant antitumor role through opsonization of target antigens and T-cell recruitment. Macrophages also form an important subset of innate immunity (M1-macrophages) while participating in the immune-stimulation context. Finally, OC has shown to engage a significant natural-killer-cells immune response, exerting direct cytotoxicity without prior sensitization. Despite this initial cytotoxicity, OC cells develop various strategies to induce an immune-tolerant state. To this end, multiple immunosuppressive molecules are secreted to impair cytotoxic cells, recruit regulatory cells, alter antigen presentation, and effectively evade immune response. Consequently, OC TME is predominantly infiltrated by immunosuppressive cells such as FOXP3
regulatory T-cells, M2-polarized macrophages and myeloid-derived suppressor cells. Despite this strong immunosuppressive state, PD-1/PD-L1 inhibitors have failed to improve outcomes. Beyond PD-1/PD-L1, OC expresses multiple other immune checkpoints that contribute to immune evasion, and each representing potential immune targets. Novel immunotherapies are attempting to overcome the immunosuppressive state and induce specific immune responses using antibodies adoptive cell therapy or vaccines. Overall, the OC TME presents both opportunities and obstacles. Immunotherapeutic approaches continue to show promise, and next-generation inhibitors offer exciting opportunities. However, tailoring therapies to individual immune characteristics will be critical for the success of these treatments.</abstract><cop>Switzerland</cop><pub>Frontiers Media S.A</pub><pmid>38164130</pmid><doi>10.3389/fimmu.2023.1328651</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | adoptive cell therapy Female Humans immune microenvironment Immunology Immunosuppressive Agents - pharmacology Immunotherapy Lymphocytes, Tumor-Infiltrating ovarian cancer Ovarian Neoplasms - therapy Programmed Cell Death 1 Receptor T-Lymphocytes, Cytotoxic Tumor Microenvironment tumor-associated macrophages tumor-infiltrating lymphocytes |
title | Targeting the immune microenvironment for ovarian cancer therapy |
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