{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:02:42Z","timestamp":1790960562928,"version":"4.1.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T00:00:00Z","timestamp":1639008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003995","name":"Natural Science Foundation of Anhui Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Immune checkpoint inhibitors (ICIs), including antibodies targeting programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1), are being extensively used on advanced human malignancies therapy. The treatment with ICIs have acquired durable tumor inhibition and changed the treatment landscape in lung cancer. Immune-related adverse events including pneumonitis and thyroiditis have been well described, but less frequent events, such as ICIs-induced thrombocytopenia, are now emerging and may sometimes be severe or fatal. Since early detection and prompt intervention are crucial to prevent fatal consequences, it is of outmost importance that medical staff is aware of these potential toxicities and learn to recognize and treat them adequately. This review focuses on the epidemiology, clinical presentation, mechanisms, and clinical management of ICIs-induced thrombocytopenia in patients with lung cancer. We also present a patient with advanced lung adenocarcinoma who received the PD-L1 inhibitor atezolizumab and eventually developed severe thrombocytopenia. The case indirectly suggests that cytokine changes might contribute to immune dysregulation in ICIs-induced thrombocytopenia.<\/jats:p>","DOI":"10.3389\/fimmu.2021.790051","type":"journal-article","created":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T11:10:30Z","timestamp":1639048230000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Immune Thrombocytopenia Induced by Immune Checkpoint Inhibitrs in Lung Cancer: Case Report and Literature Review"],"prefix":"10.3389","volume":"12","author":[{"given":"Wang","family":"Xie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"NaNa","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LeJie","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2021.1867100","article-title":"Safety of Current Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer","volume":"20","author":"Abdayem","year":"2021","journal-title":"Expert Opin Drug Saf"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2019.10.021","article-title":"Safety and Patient-Reported Outcomes of Atezolizumab, Carboplatin, and Etoposide in Extensive-Stage Small-Cell Lung Cancer (Impower133): A Randomized Phase I\/Iii Trial","volume":"31","author":"Mansfield","year":"2020","journal-title":"Ann Oncol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/onco.13553","article-title":"Nivolumab-Induced Thrombotic Thrombocytopenic Purpura in a Patient With Anal Squamous Cell Carcinoma: A Lesson on Hematologic Toxicity From Immunotherapy","volume":"25","author":"Gergi","year":"2020","journal-title":"Oncologist"},{"key":"B4","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1186\/s40425-018-0384-0","article-title":"Severe Hemophagocytic Lymphohistiocytosis in a Melanoma Patient Treated With Ipilimumab + Nivolumab","volume":"6","author":"Hantel","year":"2018","journal-title":"J Immunother Cancer"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.21037\/tlcr-21-464","article-title":"Immune-Related Adverse Event Profile of Combination Treatment of Pd-(L)1 Checkpoint Inhibitors and Bevacizumab in Non-Small Cell Lung Cancer Patients: Data From the Fda Adverse Event Reporting System","volume":"10","author":"Bai","year":"2021","journal-title":"Transl Lung Cancer Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2020.05.015","article-title":"Eltrombopag Olamine for Refractory Immune-Related Thrombocytopenia Induced by Pembrolizumab in a Non-Small Cell Lung Cancer Patient","volume":"146","author":"Ito","year":"2020","journal-title":"Lung Cancer"},{"key":"B7","doi-asserted-by":"publisher","first-page":"100871","DOI":"10.1016\/j.rmcr.2019.100871","article-title":"Immune Thrombocytopenia Induced by Nivolumab in a Patient With Non-Small Cell Lung Cancer","volume":"28","author":"Mori","year":"2019","journal-title":"Respir Med Case Rep"},{"key":"B8","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1186\/s13256-019-2245-y","article-title":"Nivolumab-Related Severe Thrombocytopenia in a Patient With Relapsed Lung Adenocarcinoma: A Case Report and Review of the Literature","volume":"13","author":"Hasegawa","year":"2019","journal-title":"J Med Case Rep"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.530478","article-title":"Immune Thrombocytopenia Induced by Immune Checkpoint Inhibitors in Solid Cancer: Case Report and Literature Review","volume":"10","author":"Liu","year":"2020","journal-title":"Front Oncol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.21873\/invivo.11852","article-title":"Severe Thrombocytopenia Associated With Pembrolizumab in Patients With Non-Small Cell Lung Cancer (Nsclc): A Case Report and Literature Review","volume":"34","author":"Mouri","year":"2020","journal-title":"In Vivo"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1177\/1078155219887212","article-title":"Pembrolizumab-Induced Thrombotic Thrombocytopenic Purpura","volume":"26","author":"Dickey","year":"2020","journal-title":"J Oncol Pharm Pract"},{"key":"B12","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.ejca.2019.08.003","article-title":"Eltrombopag Treatment for Severe Refractory Thrombocytopenia Caused by Pembrolizumab","volume":"121","author":"Song","year":"2019","journal-title":"Eur J Cancer"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1177\/1078155220913081","article-title":"Possible Atezolizumab-Associated Acute Kidney Injury and Immune Thrombocytopenia","volume":"26","author":"Y\u0131lmaz","year":"2020","journal-title":"J Oncol Pharm Pract"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3960\/jslrt.20047","article-title":"Acquired Amegakaryocytic Thrombocytopenia After Durvalumab Administration","volume":"61","author":"Suyama","year":"2021","journal-title":"J Clin Exp Hematop"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2018.02.018","article-title":"Nivolumab-Induced Severe Pancytopenia in a Patient With Lung Adenocarcinoma","volume":"119","author":"Tokumo","year":"2018","journal-title":"Lung Cancer"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.21037\/apm-21-794","article-title":"Delayed Thrombocytopenia as a Rare But Serious Adverse Event Secondary to Immune Checkpoint Inhibitor: A Case Report","volume":"10","author":"Zhou","year":"2021","journal-title":"Ann Palliat Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1177\/1078155220981155","article-title":"Delayed Immune Thrombocytopenia After Discontinuation of Nivolumab Therapy: A Case Report and Literature Review","volume":"27","author":"Fu","year":"2021","journal-title":"J Oncol Pharm Pract"},{"key":"B18","doi-asserted-by":"publisher","first-page":"85","DOI":"10.2217\/imt-2017-0100","article-title":"Immune-Mediated Thrombocytopenia and Hypothyroidism in a Lung Cancer Patient Treated With Nivolumab","volume":"10","author":"Jotatsu","year":"2018","journal-title":"Immunotherapy-Uk"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1159\/000477968","article-title":"Immune Thrombocytopenia Induced by Nivolumab in a Metastatic Non-Small Cell Lung Cancer Patient","volume":"40","author":"Karakas","year":"2017","journal-title":"Oncol Res Treat"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrc.2016.02.009","article-title":"Immune Thrombocytopenia Exacerbated by Nivolumab in a Patient With Non-Small-Cell Lung Cancer","volume":"6","author":"Bagley","year":"2016","journal-title":"Cancer Treat Commun"},{"key":"B21","doi-asserted-by":"publisher","first-page":"392","DOI":"10.6004\/jadpro.2021.12.4.4","article-title":"Management of Hematologic Adverse Events Associated With Immune Checkpoint Inhibitors","volume":"12","author":"Rogers","year":"2021","journal-title":"J Adv Pract Oncol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s40425-017-0210-0","article-title":"Thrombocytopenia in Patients With Melanoma Receiving Immune Checkpoint Inhibitor Therapy","volume":"5","author":"Shiuan","year":"2017","journal-title":"J Immunother Cancer"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(18)30175-3","article-title":"Haematological Immune-Related Adverse Events Induced by Anti-Pd-1 or Anti-Pd-L1 Immunotherapy: A Descriptive Observational Study","volume":"6","author":"Delanoy","year":"2019","journal-title":"Lancet Haematol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.ejca.2019.07.014","article-title":"Haematological Immune-Related Adverse Events With Immune Checkpoint Inhibitors, How to Manage","volume":"122","author":"Michot","year":"2019","journal-title":"Eur J Cancer"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2018-0574","article-title":"Hematologic Complications of Immune Checkpoint Inhibitors","volume":"24","author":"Davis","year":"2019","journal-title":"Oncologist"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2019.02.006","article-title":"A Case of Immune Thrombocytopaenia Induced by Pembrolizumab in a Metastatic Melanoma Patient With a History of Immune-Mediated Pure Red Cell Aplasia","volume":"112","author":"Berger","year":"2019","journal-title":"Eur J Cancer"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx159","article-title":"Idiopathic Thrombocytopenic Purpura and Autoimmune Neutropenia Induced by Prolonged Use of Nivolumab in Hodgkin\u2019s Lymphoma","volume":"28","author":"Bulbul","year":"2017","journal-title":"Ann Oncol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.cllc.2019.02.006","article-title":"Correlations Between the Immune-Related Adverse Events Spectrum and Efficacy of Anti-Pd1 Immunotherapy in Nsclc Patients","volume":"20","author":"Cortellini","year":"2019","journal-title":"Clin Lung Cancer"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.rx.2019.06.004","article-title":"Immune-Related Adverse Events as Predictors of Response in Cancer Patients Undergoing Immunotherapy","volume":"62","author":"Ezponda","year":"2020","journal-title":"Radiol (Engl Ed)"},{"key":"B30","doi-asserted-by":"publisher","first-page":"O581","DOI":"10.2144\/fsoa-2020-0021","article-title":"Development of Thrombocytopenia Is Associated With Improved Survival in Patients Treated With Immunotherapy","volume":"6","author":"Assi","year":"2020","journal-title":"Future Sci OA"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyu222","article-title":"Treatment Possibilities of Ipilimumab-Induced Thrombocytopenia\u2013Case Study and Literature Review","volume":"45","author":"Kopeck\u00fd","year":"2015","journal-title":"Jpn J Clin Oncol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.25446","article-title":"Pd-L1 Is Expressed on Human Platelets and Is Affected by Immune Checkpoint Therapy","volume":"9","author":"Rolfes","year":"2018","journal-title":"Oncotarget"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2015.06.005","article-title":"Immune-Mediated Adverse Events of Anticytotoxic T Lymphocyte-Associated Antigen 4 Antibody Therapy in Metastatic Melanoma","volume":"166","author":"Quirk","year":"2015","journal-title":"Transl Res"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.17387","article-title":"Immune Thrombocytopenia After Immune Checkpoint Inhibitor Therapy","volume":"193","author":"Amanam","year":"2021","journal-title":"Br J Haematol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00454","article-title":"Hematological Side Effects of Immune Checkpoint Inhibitors: The Example of Immune-Related Thrombocytopenia","volume":"10","author":"Calvo","year":"2019","journal-title":"Front Pharmacol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.77.6385","article-title":"Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline","volume":"36","author":"Brahmer","year":"2018","journal-title":"J Clin Oncol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.41.6750","article-title":"Management of Immune-Related Adverse Events and Kinetics of Response With Ipilimumab","volume":"30","author":"Weber","year":"2012","journal-title":"J Clin Oncol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.15085","article-title":"Pdcd1 and Ctla4 Polymorphisms Affect the Susceptibility to, and Clinical Features of, Chronic Immune Thrombocytopenia","volume":"180","author":"Kasamatsu","year":"2018","journal-title":"Br J Haematol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V91.10.3616","article-title":"Clinical Significance of Hla-Drb1*0410 in Japanese Patients With Idiopathic Thrombocytopenic Purpura","volume":"91","author":"Nomura","year":"1998","journal-title":"Blood"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.790051\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T11:10:33Z","timestamp":1639048233000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.790051\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,9]]},"references-count":39,"alternative-id":["10.3389\/fimmu.2021.790051"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.790051","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,9]]},"article-number":"790051"}}