{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:42:58Z","timestamp":1790228578618,"version":"4.1.0"},"reference-count":18,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,7,29]],"date-time":"2023-07-29T00:00:00Z","timestamp":1690588800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chung Gang Memorial Hospital","award":["CMRPG2F0231"],"award-info":[{"award-number":["CMRPG2F0231"]}]},{"name":"Chung Gang Memorial Hospital","award":["CMRPG2A0483"],"award-info":[{"award-number":["CMRPG2A0483"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The immune checkpoint inhibitor\/tyrosine kinase inhibitor (ICI\/TKI) combination treatment is currently the first-line treatment for metastatic renal cell carcinoma (mRCC). However, its efficacy beyond the third-line setting is expected to be relatively poor, and high-grade toxicities can develop by prior exposure to multiple drugs, resulting in a relatively poor performance in patients. Determining the best treatment regimen and sequence remains difficult and requires further investigation in patients with mRCC. In this study, two cases of mRCC, who failed several lines of TKI and nivolumab but exhibited a good anticancer effect after rechallenging with axitinib, are described. Both patients had a faster time to best response and better progression-free survival (PFS) than during previous treatments. Moreover, the axitinib dose could be reduced to 2.5 mg daily when used in combination with nivolumab while continuing to exert an impressive anticancer effect. To determine the cytotoxic effect, we performed a lymphocyte activation test and found that the level of granzyme B released by cytotoxic T lymphocytes and natural killer cells was higher when axitinib was combined with nivolumab. To evaluate this result, a bioinformatics approach was used to analyze the PRISM database. In conclusion, based on the results of a lymphocyte activation test and PD-1 expression, our findings indicate that sequential therapy with axitinib rechallenge after nivolumab resistance is reasonable for the treatment of mRCC.<\/jats:p>","DOI":"10.3390\/ijms241512149","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T01:26:40Z","timestamp":1690766800000},"page":"12149","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Axitinib Rechallenge Restores the Anticancer Effect after Nivolumab: A Case Report"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5182-7911","authenticated-orcid":false,"given":"Yueh-Shih","family":"Chang","sequence":"first","affiliation":[{"name":"Hemato-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, College of Medicine, Keelung & Chang Gung University, Taoyuan 33302, Taiwan"},{"name":"Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5006-0277","authenticated-orcid":false,"given":"Pei-Hung","family":"Chang","sequence":"additional","affiliation":[{"name":"Hemato-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, College of Medicine, Keelung & Chang Gung University, Taoyuan 33302, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deng-Huang","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7378-4235","authenticated-orcid":false,"given":"Chun-Bing","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan"},{"name":"Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taipei, Linkou, Keelung 833301, Taiwan"},{"name":"Taiwan Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 330036, Taiwan"},{"name":"Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Ying F.","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan"},{"name":"Institute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.6004\/jnccn.2020.0043","article-title":"NCCN Guidelines Insights: Kidney Cancer, Version 1.2021","volume":"18","author":"Motzer","year":"2020","journal-title":"J. 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