{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T05:31:45Z","timestamp":1792474305956,"version":"4.5.0"},"reference-count":30,"publisher":"American Medical Association (AMA)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"\n Importance<\/jats:title>\n Progressive multifocal leukoencephalopathy (PML) is a life-threatening demyelinating disease caused by reactivation of the JC virus (JCV) in immunocompromised patients. While immune checkpoint inhibitors (ICIs) show therapeutic potential, responses vary and predictive biomarkers are lacking.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To determine whether pretreatment JCV- and\/or BK virus\u2013specific T cells in the blood are associated with treatment efficacy.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This retrospective cohort study included 111 patients with PML who were treated with ICIs stratified by peripheral virus-specific T cell presence (ELISpot\/flow cytometry) between August 2021 and May 2024, with a median (IQR) follow-up of 7 (1-13) months. Of 112 patients with definite PML across 39 centers, 1 patient refused participation; 111 patients were included.<\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n Patients received pembrolizumab (n\u2009=\u200981), nivolumab (n\u2009=\u200928), or atezolizumab (n\u2009=\u20092) per availability and prescribing practices at participating centers.<\/jats:p>\n <\/jats:sec>\n \n Main Outcome and Measures<\/jats:title>\n Clinical outcomes, diagnostic parameters, and immune-related adverse events were compared; association of virus-specific T-cell responses with survival was analyzed using the Kaplan-Meier method.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The study cohort consisted of 111 patients (median [IQR] age, 61 [50-70] years; 74 male [66.6%]). Twenty-one patients had detectable virus-specific T cells prior to therapy, 22 were T cell\u2013negative and 68 had an unknown T-cell status. T cell\u2013positive patients showed significantly higher response rates and improved survival compared to both T cell\u2013negative patients (18\/21 [86%] vs 5\/22 [23%];\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001; median survival time, none [95% CI, undefined] vs 136.5 days [95% CI, 19 to \u221e];\n P<\/jats:italic>\n \u2009=\u2009.002) and those with unknown T-cell status (18\/21 [86%] vs 29\/68 [43%];\n P<\/jats:italic>\n \u2009=\u2009.001; median survival time, none vs 162 days [95% CI, 66 to \u221e];\n P<\/jats:italic>\n \u2009=\u2009.004). They achieved better functional outcomes (median [IQR] modified Rankin Scale score, 3 [2-4] vs 4 [3-6];\n P<\/jats:italic>\n \u2009=\u2009.009) and lower JC viral load in cerebrospinal fluid (median [IQR], 0 copies\/mL [0-502.5] vs 2500 copies\/mL [0-6900];\n P<\/jats:italic>\n \u2009=\u2009.01) during follow-up compared to T cell\u2013negative patients. Immune-related adverse events were most frequent in T cell\u2013negative patients (10\/20 [50%]), including the most severe events, and least frequent in T cell\u2013positive patients (2\/20 [10%]) (\n P<\/jats:italic>\n \u2009=\u2009.02).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n Preexisting functional virus-specific T cells were associated with better clinical response, longer survival, and lower toxicity in PML. These findings suggest the likely importance of preexisting antiviral immunity for successful ICI therapy.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaneurol.2025.5318","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T16:00:52Z","timestamp":1768924852000},"page":"280","source":"Crossref","is-referenced-by-count":8,"title":["Virus-Specific T Cells and Response to Checkpoint Inhibitors in Progressive Multifocal Leukoencephalopathy"],"prefix":"10.1001","volume":"83","author":[{"given":"Nora","family":"M\u00f6hn","sequence":"first","affiliation":[{"name":"Department of Neurology, Hannover Medical School, Hannover, Germany"},{"name":"Center of Neurology, Department of Neuroimmunology, University Hospital and University Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Grote-Levi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes","family":"Bonifacius","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Tischer-Zimmermann","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Nay","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin Fritz","family":"Jendretzky","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mieke Luise","family":"Sassmann","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Karacondi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Zent","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz Felix","family":"Konen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt-Wolfram","family":"S\u00fchs","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven G.","family":"Meuth","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich Heine University D\u00fcsseldorf, D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Pawlitzki","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich Heine University D\u00fcsseldorf, D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens","family":"Warnke","sequence":"additional","affiliation":[{"name":"Department of Neurology, Philipps University Marburg, 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