{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T11:00:15Z","timestamp":1788346815569,"version":"build-2803163510"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"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:p>Leptomeningeal metastasis (LM) is a fatal complication of malignant tumors with limited treatment options. Finding more effective therapeutic strategies is of significant importance. This case reports an LM patient from breast cancer treated with intrathecal pemetrexed (15 mg) combined with PD-1 inhibitors (40 mg). The pemetrexed dosing regimen included an induction phase (twice weekly for 2 weeks), a consolidation phase (once weekly for 4 weeks), and a maintenance phase (once monthly). The PD-1 inhibitor dosing regimen included an induction phase (once every 2 weeks for 6 weeks) and a maintenance phase (once monthly). The patient showed good tolerance, with no severe adverse events observed, and achieved favorable therapeutic outcomes, including complete resolution of neurological symptoms, negative conversion of cerebrospinal fluid cytology, and significant reduction of imaging-detected lesions. This case provides a new approach to the treatment of LM, suggesting that intrathecal immunotherapy combined with intrathecal chemotherapy may be a safe and effective treatment option, offering valuable insights for future clinical applications.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1567324","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T05:25:45Z","timestamp":1745472345000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Intrathecal administration of PD-1 inhibitor combined with pemetrexed for leptomeningeal metastases from breast cancer: a case report"],"prefix":"10.3389","volume":"16","author":[{"given":"Yushan","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guozi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaomiao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"Tai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1097\/WCO.0000000000000393","article-title":"Leptomeningeal metastases of solid cancer","volume":"29","author":"Le Rhun","year":"2016","journal-title":"Curr Opin Neurol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2016.12.006","article-title":"Leptomeningeal carcinomatosis in non-small cell lung cancer patients: A continuing challenge in the personalized treatment era","volume":"53","author":"Remon","year":"2017","journal-title":"Cancer Treat Rev"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30689-7","article-title":"Leptomeningeal metastases in non-small-cell lung cancer","volume":"19","author":"Cheng","year":"2018","journal-title":"Lancet Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13040732","article-title":"The underlying biology and therapeutic vulnerabilities of leptomeningeal metastases in adult solid cancers","volume":"13","author":"Dankner","year":"2021","journal-title":"Cancers"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.3390\/ijms17071074","article-title":"Molecular targeted therapies for the treatment of leptomeningeal carcinomatosis: current evidence and future directions","volume":"17","author":"Lee","year":"2016","journal-title":"Int J Mol Sci"},{"key":"B6","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.critrevonc.2019.01.020","article-title":"Leptomeningeal carcinomatosis in patients with breast cancer","volume":"135","author":"Franzoi","year":"2019","journal-title":"Crit Rev Oncol Hematol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/tbj.13433","article-title":"Breast cancer patients with brain metastases or leptomeningeal disease: 10-year results of a national cohort with validation of prognostic indexes","volume":"25","author":"Znidaric","year":"2019","journal-title":"Breast J"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2021.100150","article-title":"Breast cancer patients treated with intrathecal therapy for leptomeningeal metastases in a large real-life database","volume":"6","author":"Carausu","year":"2021","journal-title":"ESMO Open"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.00838","article-title":"A pilot phase 1 study of intrathecal pemetrexed for refractory leptomeningeal metastases from non-small-cell lung cancer","volume":"9","author":"Pan","year":"2019","journal-title":"Front Oncol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn112152-20200711-00647","article-title":"Clinical trials on intrathecal pemetrexed treated leptomeningeal metastases from solid tumors","volume":"44","author":"Pan","year":"2022","journal-title":"Zhonghua Zhong Liu Za Zhi"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02392-7","article-title":"Pembrolizumab in brain metastases of diverse histologies: phase 2 trial results","volume":"29","author":"Brastianos","year":"2023","journal-title":"Nat Med"},{"key":"B12","doi-asserted-by":"publisher","first-page":"5954","DOI":"10.1038\/s41467-021-25859-y","article-title":"Phase II study of ipilimumab and nivolumab in leptomeningeal carcinomatosis","volume":"12","author":"Brastianos","year":"2021","journal-title":"Nat Commun"},{"key":"B13","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1038\/s41591-022-02170-x","article-title":"Concurrent intrathecal and intravenous nivolumab in leptomeningeal disease: phase 1 trial interim results","volume":"29","author":"Glitza Oliva","year":"2023","journal-title":"Nat Med"},{"key":"B14","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1007\/s00280-012-1929-4","article-title":"Cerebrospinal fluid concentration of gefitinib and erlotinib in patients with non-small cell lung cancer","volume":"70","author":"Togashi","year":"2012","journal-title":"Cancer Chemother Pharmacol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.34.15_suppl.e20596","article-title":"Phase II study of erlotinib in advanced non-small cell lung cancer patients with leptomeningeal metastasis","volume":"34","author":"Nosaki","year":"2016","journal-title":"J Clin Oncol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"vi428","DOI":"10.1093\/annonc\/mdw383.41","article-title":"Afatinib efficacy and cerebrospinal fluid concentration in NSCLC patients with EGFR mutation developing leptomeningeal carcinomatosis","volume":"27","author":"Tamiya","year":"2016","journal-title":"Ann Oncol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.lungcan.2022.09.013","article-title":"Leptomeningeal metastases in non-small cell lung cancer: Diagnosis and treatment","volume":"174","author":"Wang","year":"2022","journal-title":"Lung Cancer"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b01073","article-title":"Discovery and evaluation of clinical candidate AZD3759, a potent, oral active, central nervous system-penetrant, epidermal growth factor receptor tyrosine kinase inhibitor","volume":"58","author":"Zeng","year":"2015","journal-title":"J Med Chem"},{"key":"B19","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1038\/s41392-024-01979-x","article-title":"Cold and hot tumors: from molecular mechanisms to targeted therapy","volume":"9","author":"Wu","year":"2024","journal-title":"Signal Transduct Target Ther"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.10.001","article-title":"Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","volume":"33","author":"Haanen","year":"2022","journal-title":"Ann Oncol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2019.10.047","article-title":"Reprogramming the T cell response to cancer by simultaneous, nanoparticle-mediated PD-L1 inhibition and immunogenic cell death","volume":"315","author":"Phung","year":"2019","journal-title":"J Controlled Release"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2017.05.024","article-title":"Cytokines in immunogenic cell death: Applications for cancer immunotherapy","volume":"97","author":"Showalter","year":"2017","journal-title":"Cytokine"},{"key":"B23","unstructured":"Neoadjuvant chemotherapy increases cytotoxic T cell, tissue resident memory T cell, and B cell infiltration in resectable NSCLC - pubMed"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2020-0994","article-title":"The abscopal effect of radiation therapy","volume":"17","author":"Craig","year":"2021","journal-title":"Future Oncol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222011061","article-title":"The abscopal effect: A review of pre-clinical and clinical advances","volume":"22","author":"Janopaul-Naylor","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B26","doi-asserted-by":"publisher","first-page":"3349","DOI":"10.1038\/s41467-019-11269-8","article-title":"Targeting photodynamic and photothermal therapy to the endoplasmic reticulum enhances immunogenic cancer cell death","volume":"10","author":"Li","year":"2019","journal-title":"Nat Commun"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.9b06040","article-title":"Near-infrared II phototherapy induces deep tissue immunogenic cell death and potentiates cancer immunotherapy","volume":"13","author":"Ma","year":"2019","journal-title":"ACS Nano"},{"key":"B28","doi-asserted-by":"publisher","first-page":"6299","DOI":"10.1038\/s41467-020-19970-9","article-title":"Tipping the immunostimulatory and inhibitory DAMP balance to harness immunogenic cell death","volume":"11","author":"Hayashi","year":"2020","journal-title":"Nature Communications"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.neo.2023.100914","article-title":"Challenges in synergizing radiotherapy with immunotherapy to unlock the abscopal effect in metastatic NSCLC: A systematic review","volume":"43","author":"Liu","year":"2023","journal-title":"Neoplasia"},{"key":"B30","doi-asserted-by":"publisher","first-page":"e28780","DOI":"10.4161\/onci.28780","article-title":"Abscopal effects of radiotherapy on advanced melanoma patients who progressed after ipilimumab immunotherapy","volume":"3","author":"Grimaldi","year":"2014","journal-title":"OncoImmunology"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1567324\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T05:25:50Z","timestamp":1745472350000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1567324\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,24]]},"references-count":30,"alternative-id":["10.3389\/fimmu.2025.1567324"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1567324","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,24]]},"article-number":"1567324"}}