{"id":"https://openalex.org/W2887723108","doi":"https://doi.org/10.1158/2326-6066.cir-18-0066","title":"Treg Fragility: A Prerequisite for Effective Antitumor Immunity?","display_name":"Treg Fragility: A Prerequisite for Effective Antitumor Immunity?","publication_year":2018,"publication_date":"2018-07-31","ids":{"openalex":"https://openalex.org/W2887723108","doi":"https://doi.org/10.1158/2326-6066.cir-18-0066","mag":"2887723108","pmid":"https://pubmed.ncbi.nlm.nih.gov/30068755","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/6080214"},"language":"en","primary_location":{"id":"doi:10.1158/2326-6066.cir-18-0066","doi":"https://doi.org/10.1158/2326-6066.cir-18-0066","is_oa":false,"landing_page_url":"https://doi.org/10.1158/2326-6066.cir-18-0066","pdf_url":null,"source":{"id":"https://openalex.org/S2765010658","display_name":"Cancer Immunology Research","issn_l":"2326-6066","issn":["2326-6066","2326-6074"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320273","host_organization_name":"American Association for Cancer Research","host_organization_lineage":["https://openalex.org/P4310320273"],"host_organization_lineage_names":["American Association for Cancer Research"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cancer Immunology Research","raw_type":"journal-article"},"volume":null,"type":"review","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6080214","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5005302353","display_name":"Abigail E. Overacre-Delgoffe","orcid":"https://orcid.org/0000-0003-4027-3487","observed_orcids":["https://orcid.org/0000-0003-4027-3487"]},"institutions":[{"id":"https://openalex.org/I170201317","display_name":"University of Pittsburgh","ror":"https://ror.org/01an3r305","country_code":"US","type":"education","lineage":["https://openalex.org/I170201317"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Abigail E. Overacre-Delgoffe","raw_affiliation_strings":["1Department of Immunology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Department of Immunology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania","institution_ids":["https://openalex.org/I170201317"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5001000053","display_name":"Dario A.A. Vignali","orcid":"https://orcid.org/0000-0002-2771-5992","observed_orcids":["https://orcid.org/0000-0002-2771-5992"]},"institutions":[{"id":"https://openalex.org/I170201317","display_name":"University of Pittsburgh","ror":"https://ror.org/01an3r305","country_code":"US","type":"education","lineage":["https://openalex.org/I170201317"]},{"id":"https://openalex.org/I4210128526","display_name":"UPMC Hillman Cancer Center","ror":"https://ror.org/03bw34a45","country_code":"US","type":"facility","lineage":["https://openalex.org/I170201317","https://openalex.org/I4210128526"]},{"id":"https://openalex.org/I4210134769","display_name":"University of Pittsburgh Medical Center","ror":"https://ror.org/04ehecz88","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210098814","https://openalex.org/I4210134769"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Dario A.A. Vignali","raw_affiliation_strings":["1Department of Immunology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania","2Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Department of Immunology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania","institution_ids":["https://openalex.org/I170201317"]},{"raw_affiliation_string":"2Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania","institution_ids":["https://openalex.org/I4210128526","https://openalex.org/I4210134769"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":0.9681,"has_fulltext":false,"cited_by_count":100,"citation_normalized_percentile":{"value":0.69363349,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":94,"max":100},"biblio":{"volume":"6","issue":"8","first_page":"882","last_page":"887"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10031","display_name":"T-cell and B-cell Immunology","score":0.6327999830245972,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10031","display_name":"T-cell and B-cell Immunology","score":0.6327999830245972,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10158","display_name":"Cancer Immunotherapy and Biomarkers","score":0.353300005197525,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10580","display_name":"Immunotherapy and Immune Responses","score":0.002099999925121665,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/regulatory-t-cells","display_name":"regulatory T cells","score":0.996999979019165},{"id":"https://openalex.org/keywords/tumor-microenvironment","display_name":"tumor microenvironment","score":0.8550000190734863},{"id":"https://openalex.org/keywords/antitumor-immunity","display_name":"antitumor immunity","score":0.796999990940094},{"id":"https://openalex.org/keywords/cancer-immunotherapy-resistance","display_name":"cancer immunotherapy resistance","score":0.7889999747276306},{"id":"https://openalex.org/keywords/immune-checkpoint-blockade","display_name":"immune checkpoint blockade","score":0.746999979019165},{"id":"https://openalex.org/keywords/foxp3","display_name":"Foxp3","score":0.871999979019165},{"id":"https://openalex.org/keywords/interferon-gamma","display_name":"interferon-gamma","score":0.984000027179718},{"id":"https://openalex.org/keywords/treg-conversion","display_name":"Treg conversion","score":0.49300000071525574},{"id":"https://openalex.org/keywords/immunosuppression","display_name":"immunosuppression","score":0.8379999995231628},{"id":"https://openalex.org/keywords/immunotherapy-response-prediction","display_name":"immunotherapy response prediction","score":0.6240000128746033}],"concepts":[{"id":"https://openalex.org/C2779727006","wikidata":"https://www.wikidata.org/wiki/Q426188","display_name":"FOXP3","level":3,"score":0.7743176221847534},{"id":"https://openalex.org/C2777701055","wikidata":"https://www.wikidata.org/wiki/Q1427096","display_name":"Immunotherapy","level":3,"score":0.7235397696495056},{"id":"https://openalex.org/C8891405","wikidata":"https://www.wikidata.org/wiki/Q1059","display_name":"Immune system","level":2,"score":0.7102378606796265},{"id":"https://openalex.org/C2776107976","wikidata":"https://www.wikidata.org/wiki/Q1786433","display_name":"Tumor microenvironment","level":3,"score":0.6695380806922913},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.6638479232788086},{"id":"https://openalex.org/C2780674031","wikidata":"https://www.wikidata.org/wiki/Q2012719","display_name":"Cancer immunotherapy","level":4,"score":0.5735620260238647},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.5273918509483337},{"id":"https://openalex.org/C2780130043","wikidata":"https://www.wikidata.org/wiki/Q192360","display_name":"Autoimmunity","level":3,"score":0.4585530459880829},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.44215822219848633},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.4406159520149231},{"id":"https://openalex.org/C2777702733","wikidata":"https://www.wikidata.org/wiki/Q1356761","display_name":"Immune tolerance","level":3,"score":0.41315317153930664},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.382598876953125},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.06812301278114319}],"mesh":[{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007167","descriptor_name":"Immunotherapy","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true},{"descriptor_ui":"D009369","descriptor_name":"Neoplasms","qualifier_ui":"Q000276","qualifier_name":"immunology","is_major_topic":true},{"descriptor_ui":"D009369","descriptor_name":"Neoplasms","qualifier_ui":"Q000628","qualifier_name":"therapy","is_major_topic":true},{"descriptor_ui":"D019139","descriptor_name":"Tumor Escape","qualifier_ui":"Q000276","qualifier_name":"immunology","is_major_topic":false},{"descriptor_ui":"D050378","descriptor_name":"T-Lymphocytes, Regulatory","qualifier_ui":"Q000276","qualifier_name":"immunology","is_major_topic":true},{"descriptor_ui":"D059016","descriptor_name":"Tumor Microenvironment","qualifier_ui":"Q000276","qualifier_name":"immunology","is_major_topic":false}],"locations_count":3,"locations":[{"id":"doi:10.1158/2326-6066.cir-18-0066","doi":"https://doi.org/10.1158/2326-6066.cir-18-0066","is_oa":false,"landing_page_url":"https://doi.org/10.1158/2326-6066.cir-18-0066","pdf_url":null,"source":{"id":"https://openalex.org/S2765010658","display_name":"Cancer Immunology Research","issn_l":"2326-6066","issn":["2326-6066","2326-6074"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320273","host_organization_name":"American Association for Cancer Research","host_organization_lineage":["https://openalex.org/P4310320273"],"host_organization_lineage_names":["American Association for Cancer Research"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cancer Immunology Research","raw_type":"journal-article"},{"id":"pmid:30068755","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/30068755","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cancer immunology research","raw_type":"Journal Article"},{"id":"pmh:oai:pubmedcentral.nih.gov:6080214","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6080214","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"Cancer Immunol Res","raw_type":"Text"}],"best_oa_location":{"id":"pmh:oai:pubmedcentral.nih.gov:6080214","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6080214","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"Cancer Immunol Res","raw_type":"Text"},"sustainable_development_goals":[{"score":0.9922999739646912,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G8811354410","display_name":"Interleukin-35 and the tumor microenvironment","funder_award_id":"R01CA203689","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"},{"id":"https://openalex.org/G9000897317","display_name":"Cancer Center Support Grant","funder_award_id":"P30CA047904","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"},{"id":"https://openalex.org/G9000901638","display_name":"Synergies among inhibitory receptors in tolerance and disease","funder_award_id":"P01AI108545","funder_id":"https://openalex.org/F4320337355","funder_display_name":"National Institute of Allergy and Infectious Diseases"}],"funders":[{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"},{"id":"https://openalex.org/F4320337351","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81"},{"id":"https://openalex.org/F4320337355","display_name":"National Institute of Allergy and Infectious Diseases","ror":"https://ror.org/043z4tv69"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":64,"referenced_works":["https://openalex.org/W1483573531","https://openalex.org/W1497240165","https://openalex.org/W1545137049","https://openalex.org/W1674079630","https://openalex.org/W1778788621","https://openalex.org/W1878828051","https://openalex.org/W1939206711","https://openalex.org/W1977165060","https://openalex.org/W1977627324","https://openalex.org/W1981528932","https://openalex.org/W1983019708","https://openalex.org/W1994160001","https://openalex.org/W2013043293","https://openalex.org/W2032166347","https://openalex.org/W2034430001","https://openalex.org/W2057373464","https://openalex.org/W2059452586","https://openalex.org/W2061071534","https://openalex.org/W2063261544","https://openalex.org/W2075326117","https://openalex.org/W2088570448","https://openalex.org/W2090069133","https://openalex.org/W2094366129","https://openalex.org/W2097811455","https://openalex.org/W2097995306","https://openalex.org/W2099738485","https://openalex.org/W2102537478","https://openalex.org/W2121080857","https://openalex.org/W2121937453","https://openalex.org/W2128856901","https://openalex.org/W2134053452","https://openalex.org/W2136573535","https://openalex.org/W2138163780","https://openalex.org/W2139226941","https://openalex.org/W2141363604","https://openalex.org/W2146409195","https://openalex.org/W2147350757","https://openalex.org/W2150678612","https://openalex.org/W2150901150","https://openalex.org/W2152642587","https://openalex.org/W2153389047","https://openalex.org/W2157669002","https://openalex.org/W2160117150","https://openalex.org/W2160834915","https://openalex.org/W2162819001","https://openalex.org/W2166075265","https://openalex.org/W2167150291","https://openalex.org/W2171775292","https://openalex.org/W2191493147","https://openalex.org/W2256893392","https://openalex.org/W2267382996","https://openalex.org/W2297581901","https://openalex.org/W2338890931","https://openalex.org/W2344037260","https://openalex.org/W2401985889","https://openalex.org/W2528854513","https://openalex.org/W2559314446","https://openalex.org/W2559849011","https://openalex.org/W2560367415","https://openalex.org/W2600304928","https://openalex.org/W2619691134","https://openalex.org/W4235343461","https://openalex.org/W6675430841","https://openalex.org/W6682156754"],"related_works":["https://openalex.org/W2802745401","https://openalex.org/W4306734484","https://openalex.org/W4308401736","https://openalex.org/W4310598731","https://openalex.org/W7134123974","https://openalex.org/W7204548277","https://openalex.org/W2619691134","https://openalex.org/W4385955972","https://openalex.org/W4402252614","https://openalex.org/W2890334478"],"abstract_inverted_index":{"Abstract":[0],"Inhibitory":[1],"checkpoint":[2],"blockade":[3],"has":[4],"significantly":[5],"improved":[6],"patient":[7],"response":[8],"rate":[9],"across":[10],"numerous":[11],"tumor":[12,29,139],"types.":[13],"However,":[14],"most":[15],"patients":[16],"remain":[17],"unresponsive":[18],"to":[19,66,92,96,132,223,231],"immunotherapy,":[20],"suggesting":[21],"that":[22,41,147,168,228],"unappreciated":[23],"mechanisms":[24,80],"of":[25,36,75,107,154,190,199],"resistance":[26],"exist.":[27],"The":[28,51],"microenvironment":[30,62],"(TME)":[31],"is":[32,53,103],"unique":[33],"and":[34,57,68,81,115,174,193,202,215,218,243],"composed":[35],"many":[37],"suppressive":[38,191],"cell":[39,76],"populations":[40,77],"inhibit":[42],"antitumor":[43,98],"immune":[44,64,113,170],"responses,":[45],"including":[46],"regulatory":[47],"T":[48],"cells":[49,65,167],"(Tregs).":[50],"TME":[52,124,214],"nutrient":[54],"poor,":[55],"acidic,":[56],"hypoxic,":[58],"creating":[59],"a":[60,72,94,127,236],"challenging":[61],"for":[63,221],"function":[67,120],"survive.":[69],"Tregs":[70,88,210,234],"suppress":[71],"wide":[73],"variety":[74],"through":[78],"multiple":[79],"are":[82,89],"tasked":[83],"with":[84],"limiting":[85],"tissue":[86,172],"damage.":[87],"now":[90],"considered":[91],"be":[93],"barrier":[95],"effective":[97],"immunity.":[99],"Systemic":[100],"Treg":[101,119,149,156,184,204],"depletion":[102],"not":[104],"favored":[105],"because":[106],"their":[108,219],"critical":[109,155],"role":[110],"in":[111,164,188],"maintaining":[112],"homeostasis":[114],"preventing":[116],"autoimmunity.":[117],"Reducing":[118],"specifically":[121],"within":[122,137],"the":[123,134,138,208,213,229],"may":[125],"provide":[126],"more":[128],"effective,":[129],"targeted":[130],"approach":[131],"limit":[133],"immunosuppressive":[135],"environment":[136],"without":[140,197],"inducing":[141],"systemic":[142],"adverse":[143],"consequences.":[144],"Targeting":[145],"molecules":[146],"cause":[148,169,182],"instability,":[150],"characterized":[151],"by":[152],"loss":[153,189,198],"transcription":[157],"factors":[158],"such":[159],"as":[160],"Foxp3,":[161],"could":[162],"result":[163],"conversion":[165],"into":[166],"pathology,":[171],"damage,":[173],"subsequent":[175],"autoimmune":[176],"side":[177],"effects.":[178],"Interferon-\u03b3":[179],"(IFN\u03b3)":[180],"can":[181],"intratumoral":[183,233],"\u201cfragility,\u201d":[185],"which":[186,232],"results":[187],"activity":[192],"increased":[194],"IFN\u03b3":[195],"production":[196],"Foxp3":[200],"expression":[201],"gross":[203],"\u201cidentity.\u201d":[205],"We":[206,226],"reviewed":[207],"impact":[209],"have":[211],"on":[212],"vice":[216],"versa,":[217],"implications":[220],"responsiveness":[222],"cancer":[224],"immunotherapy.":[225],"propose":[227],"extent":[230],"develop":[235],"\u201cfragile\u201d":[237],"phenotype":[238],"following":[239],"immunotherapy":[240],"will":[241],"predict":[242],"dictate":[244],"responsiveness.":[245],"Cancer":[246],"Immunol":[247],"Res;":[248],"6(8);":[249],"882\u20137.":[250],"\u00a92018":[251],"AACR.":[252]},"counts_by_year":[{"year":2026,"cited_by_count":11},{"year":2025,"cited_by_count":11},{"year":2024,"cited_by_count":17},{"year":2023,"cited_by_count":12},{"year":2022,"cited_by_count":11},{"year":2021,"cited_by_count":12},{"year":2020,"cited_by_count":15},{"year":2019,"cited_by_count":9},{"year":2018,"cited_by_count":2}],"updated_date":"2026-11-06T12:05:46.655746","created_date":"2018-08-22T00:00:00"}