{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T16:18:02Z","timestamp":1789402682387,"version":"build-2803163510"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The suppressive effects of immune checkpoint inhibitors (ICIs) on anti-tumor immunity have been well documented. However, ICIs can enhance immune responses and trigger autoimmune-related diseases by blocking PD-1 or PD-L1. The worst prognosis is observed in paraneoplastic neurological syndromes (PNS). This study aimed to evaluate the clinical characteristics of PD-1\/PD-L1 inhibitor\u2013related PNS and the prognostic impact of antibody subtypes, with the goal of enabling pre-treatment risk warning.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This was a retrospective descriptive study involving 224 patients with PD-1\/PD-L1 inhibitor\u2013related PNS from May 2015 to May 2025, including 8 patients who presented at our hospital and 216 patients reported in the literature. According to the July 2021 international consensus diagnostic framework for PNS, patients were stratified into risk-antibody (high-, intermediate-, and low-risk), unknown-risk antibody, and antibody-negative groups. Clinical features, primary tumor type, ICI regimen, autoantibody profile, treatments, and outcomes were analyzed. Risk-antibody subtypes were further explored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>There were 112 patients in the risk-antibody group (87 high-risk, 20 intermediate-risk, and 5 low-risk), 51 in the unknown-risk antibody group, and 61 in the antibody-negative group. The risk-antibody group showed a higher incidence of limbic encephalitis, subacute cerebellar degeneration, and subacute sensory neuronopathy. The prognosis was worse in the risk-antibody group, with a mortality rate of 29%, significantly higher than 17% in the unknown-risk group and 10% in the antibody-negative group (P = 0.012). Anti-Hu\u2013positive patients were mainly diagnosed with limbic encephalitis, encephalomyelitis, and subacute cerebellar degeneration, with a mortality rate of 23%. Anti-Ma\u2013positive patients primarily presented with encephalomyelitis, limbic encephalitis, and subacute cerebellar degeneration, with a mortality rate of 35%. Anti-Yo\u2013positive patients were mainly associated with subacute cerebellar degeneration, with a mortality rate of 25%. The mortality rate among Anti-amphiphysin\u2013positive patients was 33%. In contrast, 71% of Anti-NMDAR\u2013positive patients had favorable outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Among patients with PD-1\/PD-L1 inhibitor\u2013related PNS, those with risk-antibody positivity had worse prognoses, while patients with unknown-risk antibodies had outcomes similar to those with antibody negativity, suggesting that unknown-risk antibodies are not directly pathogenic or may elicit weaker immune responses. Pre-treatment screening for PNS-related antibodies is recommended, as it may facilitate early warning, identify high-risk patients, and help prevent autoimmune-related diseases caused by excessive immune modulation. After disease onset, efficient immunomodulatory treatment tailored to antibody subtypes may improve outcomes in risk-antibody\u2013positive patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1670751","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T06:45:32Z","timestamp":1766040332000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of warning strategies for paraneoplastic neurological syndromes associated with PD-1\/PD-L1 inhibitors"],"prefix":"10.3389","volume":"16","author":[{"given":"Zhuangzhuang","family":"Ren","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yudan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguo","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaokun","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenjing","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s13760-020-01564-3","article-title":"Paraneoplastic syndrome or immune-related adverse event? 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