{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:00:52Z","timestamp":1760238052263,"version":"build-2065373602"},"reference-count":38,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T00:00:00Z","timestamp":1657843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dong-A University","award":["2022"],"award-info":[{"award-number":["2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: With the development of immunology, immune checkpoint inhibitors (ICIs) have been widely used in various cancer treatments. Although some patients can benefit from ICIs, other patients have no response to ICIs or suffer from hyperprogression. There has been no biomarker for predicting the efficacy of ICIs. Thus, the objective of this study was to find biomarkers for predicting the efficacy of ICIs using peripheral blood. Methods: Adults patients planned to be treated with ICIs were enrolled in this study. Blood sampling was carried out before and after administration of ICIs. Changes of immune cell fraction were analyzed for each patient. Results: Among 182 patients enrolled, immune cell analysis was performed for 90 patients. The objective response rate was 14.4% (n = 13\/90). The median progression-free survival (PFS) was 6.0 months (95% CI: 3.1\u20138.9 months), and the median overall survival (OS) was 13.9 months (95% CI: 5.6\u201322.2 months). Significant benefits in ORR and OS were shown for patients with increased NKp46-\/CD56+ NK cells (p = 0.033 and p = 0.013, respectively). The PFS tended to be longer in these patients, although the difference was not statistically significant (p = 0.050). Conclusion: Changes of immune cell fraction before and after administration of ICIs could be a novel biomarker for predicting the efficacy of immunotherapy.<\/jats:p>","DOI":"10.3390\/cancers14143440","type":"journal-article","created":{"date-parts":[[2022,7,17]],"date-time":"2022-07-17T21:00:28Z","timestamp":1658091628000},"page":"3440","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Changes of Immune Cell Fractions in Patients Treated with Immune Checkpoint Inhibitors"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5566-378X","authenticated-orcid":false,"given":"Hye Ryeon","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Dong-A University College of Medicine, Busan 49201, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung Hun","family":"Kang","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju 52727, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Dong-A University College of Medicine, Busan 49201, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung Tae","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilhwan","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan 48108, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Joo","family":"Min","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seong Hoon","family":"Shin","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Kosin University Gospel Hospital, Busan 49267, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8321-4113","authenticated-orcid":false,"given":"Sung Yong","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Dong-A University College of Medicine, Busan 49201, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1781-2262","authenticated-orcid":false,"given":"Gyeong-Won","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju 52727, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Hyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Dong-A University College of Medicine, Busan 49201, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun Ho","family":"Ji","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon 51353, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seok Jae","family":"Huh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Dong-A University College of Medicine, Busan 49201, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suee","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Dong-A University College of Medicine, Busan 49201, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1056\/NEJMoa011954","article-title":"Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer","volume":"346","author":"Schiller","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1016\/j.clinthera.2016.03.026","article-title":"Current Challenges in Cancer Treatment","volume":"38","author":"Zugazagoitia","year":"2016","journal-title":"Clin. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.3389\/fphar.2018.01300","article-title":"Evolution of Cancer Pharmacological Treatments at the Turn of the Third Millennium","volume":"9","author":"Falzone","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.3389\/fimmu.2020.02023","article-title":"Predictive Biomarkers of Immune Checkpoint Inhibitors-Related Toxicities","volume":"11","author":"Xu","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1056\/NEJMoa1003466","article-title":"Improved survival with ipilimumab in patients with metastatic melanoma","volume":"363","author":"Hodi","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1186\/s13045-017-0541-9","article-title":"Recent development in clinical applications of PD-1 and PD-L1 antibodies for cancer immunotherapy","volume":"10","author":"Liu","year":"2017","journal-title":"J. Hematol. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"561","DOI":"10.3389\/fphar.2017.00561","article-title":"PD-1 and PD-L1 Checkpoint Signaling Inhibition for Cancer Immunotherapy: Mechanism, Combinations, and Clinical Outcome","volume":"8","author":"Alsaab","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e5539","DOI":"10.1097\/MD.0000000000005539","article-title":"A meta-analysis of efficacy and safety of antibodies targeting PD-1\/PD-L1 in treatment of advanced nonsmall cell lung cancer","volume":"95","author":"Wang","year":"2016","journal-title":"Medicine"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1056\/NEJMoa1501824","article-title":"Pembrolizumab for the treatment of non-small-cell lung cancer","volume":"372","author":"Garon","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/nature14011","article-title":"Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients","volume":"515","author":"Herbst","year":"2014","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.jtho.2016.11.2228","article-title":"PD-L1 Immunohistochemistry Assays for Lung Cancer: Results from Phase 1 of the Blueprint PD-L1 IHC Assay Comparison Project","volume":"12","author":"Hirsch","year":"2017","journal-title":"J. Thorac. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1158\/1535-7163.MCT-14-0983","article-title":"PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy","volume":"14","author":"Patel","year":"2015","journal-title":"Mol. Cancer Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e000442","DOI":"10.1136\/esmoopen-2018-000442","article-title":"Implementing TMB measurement in clinical practice: Considerations on assay requirements","volume":"4","author":"Longshore","year":"2019","journal-title":"ESMO Open"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/s41588-018-0312-8","article-title":"Tumor mutational load predicts survival after immunotherapy across multiple cancer types","volume":"51","author":"Samstein","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e126908","DOI":"10.1172\/jci.insight.126908","article-title":"PD-L1 expression and tumor mutational burden are independent biomarkers in most cancers","volume":"4","author":"Yarchoan","year":"2019","journal-title":"JCI Insight"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s13045-019-0738-1","article-title":"Mismatch repair deficiency\/microsatellite instability-high as a predictor for anti-PD-1\/PD-L1 immunotherapy efficacy","volume":"12","author":"Zhao","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-018-0191-1","article-title":"Immune checkpoint inhibitors: Recent progress and potential biomarkers","volume":"50","author":"Darvin","year":"2018","journal-title":"Exp. Mol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1056\/NEJMoa1507643","article-title":"Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer","volume":"373","author":"Borghaei","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1084\/jem.182.2.459","article-title":"CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation","volume":"182","author":"Krummel","year":"1995","journal-title":"J. Exp. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"12293","DOI":"10.1073\/pnas.192461099","article-title":"Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade","volume":"99","author":"Iwai","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1126\/science.271.5256.1734","article-title":"Enhancement of antitumor immunity by CTLA-4 blockade","volume":"271","author":"Leach","year":"1996","journal-title":"Science"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/nrc3239","article-title":"The blockade of immune checkpoints in cancer immunotherapy","volume":"12","author":"Pardoll","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1056\/NEJMoa1606774","article-title":"Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer","volume":"375","author":"Reck","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1016\/S0140-6736(15)01281-7","article-title":"Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): A randomised controlled trial","volume":"387","author":"Herbst","year":"2016","journal-title":"Lancet"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1056\/NEJMoa1613683","article-title":"Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma","volume":"376","author":"Bellmunt","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S1470-2045(16)00175-3","article-title":"Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): A multicentre, open-label, phase 1b trial","volume":"17","author":"Muro","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1200\/JCO.19.03136","article-title":"Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non-Small-Cell Lung Cancer","volume":"38","author":"Gadgeel","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.1056\/NEJMoa1613493","article-title":"First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer","volume":"376","author":"Carbone","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1016\/S0140-6736(16)00561-4","article-title":"Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: A single-arm, multicentre, phase 2 trial","volume":"387","author":"Rosenberg","year":"2016","journal-title":"Lancet"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1200\/JCO.21.02010","article-title":"Artificial Intelligence-Powered Spatial Analysis of Tumor-Infiltrating Lymphocytes as Complementary Biomarker for Immune Checkpoint Inhibition in Non-Small-Cell Lung Cancer","volume":"40","author":"Park","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3338","DOI":"10.1172\/JCI80004","article-title":"From mice to humans: Developments in cancer immunoediting","volume":"125","author":"Teng","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1016\/j.cell.2016.01.049","article-title":"The Basis of Oncoimmunology","volume":"164","author":"Palucka","year":"2016","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/imcb.1003","article-title":"Immune checkpoint inhibitors in cancer therapy: A focus on T-regulatory cells","volume":"96","author":"Elkord","year":"2018","journal-title":"Immunol. Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/S1471-4906(01)02060-9","article-title":"The biology of human natural killer-cell subsets","volume":"22","author":"Cooper","year":"2001","journal-title":"Trends Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1084\/jem.186.7.1129","article-title":"p46, a novel natural killer cell-specific surface molecule that mediates cell activation","volume":"186","author":"Sivori","year":"1997","journal-title":"J. Exp. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"107.e4","DOI":"10.1016\/j.immuni.2017.12.007","article-title":"NKp46 Receptor-Mediated Interferon-\u03b3 Production by Natural Killer Cells Increases Fibronectin 1 to Alter Tumor Architecture and Control Metastasis","volume":"48","author":"Glasner","year":"2018","journal-title":"Immunity"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Murad, S., Michen, S., Becker, A., Fussel, M., Schackert, G., Tonn, T., Momburg, F., and Temme, A. (2022). NKG2C+ NK Cells for Immunotherapy of Glioblastoma Multiforme. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23105857"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1158\/1078-0432.CCR-17-1902","article-title":"Evaluation of Overall Response Rate and Progression-Free Survival as Potential Surrogate Endpoints for Overall Survival in Immunotherapy Trials","volume":"24","author":"Mushti","year":"2018","journal-title":"Clin. Cancer Res."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/14\/3440\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:51:06Z","timestamp":1760140266000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/14\/3440"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,15]]},"references-count":38,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["cancers14143440"],"URL":"https:\/\/doi.org\/10.3390\/cancers14143440","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2022,7,15]]}}}