{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T05:35:42Z","timestamp":1775540142745,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K16800"],"award-info":[{"award-number":["22K16800"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Unmet challenges in systemic therapy persist for advanced renal cell carcinoma (RCC) despite the widespread use of anti\u2010angiogenetic tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). We previously showed that dipeptidyl peptidase 4 inhibitor (DPP4i) improved TKI sensitivity using patient\u2010derived RCC cells and experimental TKI\u2010resistant models. To address whether DPP4i is clinically useful for the enhancement of RCC systemic therapy, including ICIs, we analyzed 320 cases with RCC who underwent systemic therapy. Patients with DPP4i treatment exhibited longer overall survival (hazard ratio: 0.50, 95% confidence interval: 0.30\u20130.82,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0060). In the Cox proportional hazards model, the use of DPP4is, along with BMI \u2265\u200925, no metastasis, low serum lactate dehydrogenase (LDH), and low serum C\u2010reactive protein (CRP), was a favorable prognostic factor. Additionally, more pronounced tumor shrinkage was observed in a within\u2010subgroup comparison of patients receiving TKI or ICI as first\u2010line therapies. Consistently, we found that DPP4 high RCC tumors exhibit reduced immune infiltration and lower scores for effector T cell infiltration\u2010related signatures based on the RNA sequencing data from the CheckMate\u2010009, 010, and 025 studies. These findings can potentially change the interpretation of the prognostic impact of type 2 diabetes mellitus on RCC and bolster the rationale for initiating a prospective clinical trial to evaluate concurrent use of DPP4i with RCC therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1111\/cas.70250","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T16:10:35Z","timestamp":1763568635000},"page":"468-475","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Prognostic Impact of\n                    <scp>DPP4<\/scp>\n                    Inhibitors on Systemic Drug Therapy for Advanced Kidney Cancer Patients"],"prefix":"10.1111","volume":"117","author":[{"given":"Shuhei","family":"Kamada","sequence":"first","affiliation":[{"name":"Division of Systems Medicine and Gene Therapy Saitama Medical University  Saitama Japan"},{"name":"Department of Urology, Graduate School of Medicine Chiba University  Chiba Japan"},{"name":"Department of Urology, Saitama Medical Center Saitama Medical University  Saitama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sachi","family":"Kitayama","sequence":"additional","affiliation":[{"name":"Division of Systems Medicine and Gene Therapy Saitama Medical University  Saitama Japan"},{"name":"Department of Urology, Saitama Medical Center Saitama Medical University  Saitama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryosuke","family":"Yamase","sequence":"additional","affiliation":[{"name":"Division of Systems Medicine and Gene Therapy Saitama Medical University  Saitama Japan"},{"name":"Department of Urology, Graduate School of Medicine Chiba University  Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhiro","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Division of Systems Medicine and Gene Therapy Saitama Medical University  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