{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:07:15Z","timestamp":1786493235290,"version":"build-2736575974"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T00:00:00Z","timestamp":1751414400000},"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. Med."],"abstract":"<jats:p>Invasive mucormycosis contributes to a high mortality rate in patients with hematological malignancies. When it disseminates to multiple organs, especially to the brain, the prognosis is extremely poor. The traditional antifungal strategies including surgery have less efficacy in patients with hematological malignancies. Here, we describe a case report of a 62-year-old man with refractory lymphoma who developed mucormycosis caused by <jats:italic>Rhizomucor pusillus<\/jats:italic> after chemotherapy, which disseminated extensively to the lungs, diaphragm, brain and spleen. He was successfully treated with antifungal agents combined with PD-1 inhibitor, which may simultaneously exhibit efficacy in treatment of lymphoma and mucormycosis. The patient\u2019s lymphoma and mucormycosis were well controlled; ultimately, autologous hematopoietic stem cell transplantation was successfully performed, and the patient achieved long-term survival.<\/jats:p>","DOI":"10.3389\/fmed.2025.1608828","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T05:51:18Z","timestamp":1751435478000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Case Report: Immune checkpoint inhibitor exhibits dual benefits for a refractory lymphoma patient with disseminated mucormycosis"],"prefix":"10.3389","volume":"12","author":[{"given":"Qibei","family":"Teng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhizhi","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinwen","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfei","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjue","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiujie","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haowen","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,2]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"592","DOI":"10.3390\/jof9050592","article-title":"Clinical features and treatment progress of invasive mucormycosis in patients with hematological malignancies","volume":"9","author":"Yang","year":"2023","journal-title":"J Fungi"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1086\/432579","article-title":"Epidemiology and outcome of zygomycosis: a review of 929 reported cases","volume":"41","author":"Roden","year":"2005","journal-title":"Clin Infect Dis"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11046-021-00607-4","article-title":"Mucormycosis in mainland China: a systematic review of case reports","volume":"187","author":"Wei","year":"2022","journal-title":"Mycopathologia"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.cmi.2018.07.011","article-title":"The epidemiology and clinical manifestations of mucormycosis: a systematic review and meta-analysis of case reports","volume":"25","author":"Jeong","year":"2019","journal-title":"Clin Microbiol Infect"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1268840","DOI":"10.3389\/fmed.2023.1268840","article-title":"The outcome and the risk factors of mucormycosis among patients with hematological diseases: a systematic and meta-analysis","volume":"10","author":"Shen","year":"2023","journal-title":"Front Med"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1086\/590004","article-title":"Delaying amphotericin B\u2013based frontline therapy significantly increases mortality among patients with hematologic malignancy who have zygomycosis","volume":"47","author":"Chamilos","year":"2008","journal-title":"Clin Infect Dis"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e405","DOI":"10.1016\/S1473-3099(19)30312-3","article-title":"Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the mycoses study group education and research consortium","volume":"19","author":"Cornely","year":"2019","journal-title":"Lancet Infect Dis"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"433","DOI":"10.3324\/haematol.2016.152900","article-title":"ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients","volume":"102","author":"Tissot","year":"2016","journal-title":"Haematologica"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"811.e1","DOI":"10.1016\/j.cmi.2016.03.029","article-title":"Initial use of combination treatment does not impact survival of 106 patients with haematologic malignancies and mucormycosis: a propensity score analysis","volume":"22","author":"Kyvernitakis","year":"2016","journal-title":"Clin Microbiol Infect"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"5556540","DOI":"10.1155\/2023\/5556540","article-title":"Overcoming the odds: successful treatment of disseminated mucormycosis with gastrointestinal and jaw involvement in a patient with acute myeloid leukemia","volume":"2023","author":"Al-Busaidi","year":"2023","journal-title":"Case Rep Infect Dis"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1097\/MPH.0b013e3181ca0dcf","article-title":"Successful triple combination therapy of disseminated absidia corymbifera infection in an adolescent with osteosarcoma","volume":"32","author":"Roux","year":"2010","journal-title":"J Pediatr Hematol Oncol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"165","DOI":"10.3390\/jof7030165","article-title":"Disseminated mucormycosis in immunocompromised children: are new antifungal agents making a difference? A multicenter retrospective study","volume":"7","author":"Elitzur","year":"2021","journal-title":"J Fungi"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1007\/s11046-018-0287-0","article-title":"Isavuconazole in a successful combination treatment of disseminated mucormycosis in a child with acute lymphoblastic leukaemia and generalized haemochromatosis: a case report and review of the literature","volume":"184","author":"Pomorska","year":"2019","journal-title":"Mycopathologia"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1182\/blood.2018891598","article-title":"Ibrutinib plus lenalidomide and rituximab has promising activity in relapsed\/refractory non-germinal center B-cell-like DLBCL","volume":"134","author":"Goy","year":"2019","journal-title":"Blood"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"e481","DOI":"10.1016\/S2666-7568(22)00123-4","article-title":"Ibrutinib, rituximab, and lenalidomide in unfit or frail patients aged 75 years or older with de novo diffuse large B-cell lymphoma: a phase 2, single-arm study","volume":"3","author":"Xu","year":"2022","journal-title":"Lancet Healthy Longev"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1732","DOI":"10.1182\/blood-2024-207021","article-title":"Time-limited of Zanubrutinib, rituximab and Lenalidomide (ZR2) regimen for the treatment of super-elderly diffuse large B-cell lymphoma (DLBCL): a prospective, exploratory clinical study","volume":"144","author":"Zou","year":"2024","journal-title":"Blood"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1159\/000481888","article-title":"Checkpoint inhibition in non-Hodgkin's lymphoma","volume":"40","author":"He\u00df","year":"2017","journal-title":"Oncol Res Treat"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"110","DOI":"10.3760\/cma.j.cn115356-20230509-00105","article-title":"Efficacy and safety of tislelizumab combined with zanubrutinib in treatment of refractory diffuse large B-cell lymphoma","volume":"33","author":"Zuo","year":"2024","journal-title":"J Leuk Lymphoma"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1594","DOI":"10.1182\/blood-2019-125485","article-title":"An update on safety and preliminary efficacy of highly specific Bruton tyrosine kinase (BTK) inhibitor Zanubrutinib in combination with PD-1 inhibitor Tislelizumab in patients with previously treated B-cell lymphoid malignancies","volume":"134","author":"Tam","year":"2019","journal-title":"Blood"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"101636","DOI":"10.1016\/j.tranon.2023.101636","article-title":"A systematic review and meta-analysis of immune checkpoint therapy in relapsed or refractory non-Hodgkin lymphoma; a friend or foe?","volume":"30","author":"Davoodi-Moghaddam","year":"2023","journal-title":"Transl Oncol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"E966","DOI":"10.1073\/pnas.1500712112","article-title":"Therapeutic antitumor immunity by checkpoint blockade is enhanced by ibrutinib, an inhibitor of both BTK and ITK","volume":"112","author":"Sagiv-Barfi","year":"2015","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"33331","DOI":"10.18632\/oncotarget.8973","article-title":"Thalidomide enhanced the efficacy of CHOP chemotherapy in the treatment of diffuse large B cell lymphoma: a phase II study","volume":"7","author":"Ji","year":"2016","journal-title":"Oncotarget"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"109652","DOI":"10.1016\/j.cbi.2021.109652","article-title":"Thalidomide suppresses angiogenesis and immune evasion via lncRNA FGD5-AS1\/miR-454\u20133p\/ZEB1 axis-mediated VEGFA expression and PD-1\/PD-L1 checkpoint in NSCLC","volume":"349","author":"Xia","year":"2021","journal-title":"Chem Biol Interact"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"812","DOI":"10.2174\/0113892010319495241218114812","article-title":"Strengthening effect of thalidomide combined with an anti-PD1 antibody on enhancing immunity for lung Cancer therapy","volume":"26","author":"Liu","year":"2025","journal-title":"Curr Pharm Biotechnol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"111842","DOI":"10.1016\/j.jinorgbio.2022.111842","article-title":"Thalidomide-based Pt (IV) prodrugs designed to exert synergistic effect of immunomodulation and chemotherapy","volume":"232","author":"Li","year":"2022","journal-title":"J Inorg Biochem"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/j.it.2015.02.008","article-title":"Overcoming T cell exhaustion in infection and cancer","volume":"36","author":"Pauken","year":"2015","journal-title":"Trends Immunol"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/nri.2017.112","article-title":"Immune checkpoint blockade in infectious diseases","volume":"18","author":"Wykes","year":"2018","journal-title":"Nat Rev Immunol"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.1093\/infdis\/jix191","article-title":"Clinical trial of the anti-PD-L1 antibody BMS-936559 in HIV-1 infected participants on suppressive antiretroviral therapy","volume":"215","author":"Gay","year":"2017","journal-title":"J Infect Dis"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1038\/nature07662","article-title":"Enhancing SIV-specific immunity in vivo by PD-1 blockade","volume":"458","author":"Velu","year":"2009","journal-title":"Nature"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.1016\/j.immuni.2016.04.022","article-title":"Costimulatory and coinhibitory receptor pathways in infectious disease","volume":"44","author":"Attanasio","year":"2016","journal-title":"Immunity"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/j.jinf.2021.12.009","article-title":"T-cells of invasive candidiasis patients show patterns of T-cell-exhaustion suggesting checkpoint blockade as treatment option","volume":"84","author":"Mellinghoff","year":"2022","journal-title":"J Infect"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"838344","DOI":"10.3389\/fimmu.2022.838344","article-title":"Blockade of the PD-1\/PD-L1 immune checkpoint pathway improves infection outcomes and enhances fungicidal host defense in a murine model of invasive pulmonary mucormycosis","volume":"13","author":"Wurster","year":"2022","journal-title":"Front Immunol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1018202","DOI":"10.3389\/fimmu.2022.1018202","article-title":"Checkpoint inhibitors as immunotherapy for fungal infections: promises, challenges, and unanswered questions","volume":"13","author":"Wurster","year":"2022","journal-title":"Front Immunol"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1093\/infdis\/jiaa264","article-title":"Protective activity of programmed cell death protein 1 blockade and synergy with caspofungin in a murine invasive pulmonary aspergillosis model","volume":"222","author":"Wurster","year":"2020","journal-title":"J Infect Dis"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"3535","DOI":"10.4049\/jimmunol.1700840","article-title":"Anti\u2013PD-1 antibody treatment promotes clearance of persistent cryptococcal lung infection in mice","volume":"199","author":"Roussey","year":"2017","journal-title":"J Immunol"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1097\/SHK.0000000000001392","article-title":"Blockade of PD-1 attenuated post sepsis aspergillosis via the activation of IFN-\u03b3 and the dampening of IL-10","volume":"53","author":"Vu","year":"2020","journal-title":"Shock"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/S1473-3099(16)30541-2","article-title":"Nivolumab plus interferon-\u03b3 in the treatment of intractable mucormycosis","volume":"17","author":"Grimaldi","year":"2017","journal-title":"Lancet Infect Dis"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"e530","DOI":"10.1097\/HS9.0000000000000530","article-title":"Immune checkpoint blockade for aspergillosis and mucormycosis coinfection","volume":"5","author":"Banck","year":"2021","journal-title":"Hema"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.mmcr.2022.06.003","article-title":"Nivolumab and interferon-\u03b3 rescue therapy to control mixed mould and bacterial superinfection after necrotizing fasciitis and septic shock","volume":"37","author":"Lukaszewicz","year":"2022","journal-title":"Med Mycol Case Rep"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"900522","DOI":"10.3389\/fimmu.2022.900522","article-title":"Case report: immune checkpoint blockade plus interferon-\u0393 add-on antifungal therapy in the treatment of refractory covid-associated pulmonary aspergillosis and cerebral mucormycosis","volume":"13","author":"Serris","year":"2022","journal-title":"Front Immunol"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"116653","DOI":"10.1016\/j.diagmicrobio.2024.116653","article-title":"Combined antifungal therapy with immunostimulation for refractory cutaneous and peritoneal mucormycosis caused by Rhizopus microsporus","volume":"111","author":"Mhenni","year":"2025","journal-title":"Diagn Microbiol Infect Dis"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"809","DOI":"10.3109\/08820139.2011.615877","article-title":"Immunomodulatory properties of antifungal agents on phagocytic cells","volume":"40","author":"Simitsopoulou","year":"2011","journal-title":"Immunol Investig"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"R85","DOI":"10.1186\/cc12711","article-title":"Blockade ofthe negative co-stimulatory molecules PD-1 and CTLA-4 improves survival in primary and secondary fungal sepsis","volume":"17","author":"Chang","year":"2013","journal-title":"Crit Care"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1128\/AAC.01268-06","article-title":"Pretreatment with empty liposomes attenuates the immunopathology of invasive pulmonary aspergillosis in corticosteroid-immunosuppressed mice","volume":"51","author":"Lewis","year":"2007","journal-title":"Antimicrob Agents Chemother"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1097\/SHK.0b013e3182168cce","article-title":"Dose-dependent effect of anti-CTLA-4 on survival in sepsis","volume":"36","author":"Inoue","year":"2011","journal-title":"Shock"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1608828\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T05:51:21Z","timestamp":1751435481000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1608828\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,2]]},"references-count":45,"alternative-id":["10.3389\/fmed.2025.1608828"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1608828","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,2]]},"article-number":"1608828"}}