{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:16:22Z","timestamp":1792109782170,"version":"4.4.0"},"reference-count":45,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"unspecified","delay-in-days":27,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018904","name":"Beijing Xisike Clinical Oncology Research Foundation","doi-asserted-by":"publisher","award":["Y-Gilead2024-ZD-0226"],"award-info":[{"award-number":["Y-Gilead2024-ZD-0226"]}],"id":[{"id":"10.13039\/100018904","id-type":"DOI","asserted-by":"publisher"}]},{"name":"1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University","award":["ZYAI24062"],"award-info":[{"award-number":["ZYAI24062"]}]},{"DOI":"10.13039\/501100018542","name":"Natural Science Foundation of Sichuan Province","doi-asserted-by":"publisher","award":["2025ZNSFSC1870"],"award-info":[{"award-number":["2025ZNSFSC1870"]}],"id":[{"id":"10.13039\/501100018542","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Qimingxing\u201d Research Fund for Young Talents of West China Hospital","award":["HXQMX0046"],"award-info":[{"award-number":["HXQMX0046"]}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"crossref","award":["NSFC 82202901"],"award-info":[{"award-number":["NSFC 82202901"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"crossref","award":["NSFC 82373422"],"award-info":[{"award-number":["NSFC 82373422"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"crossref","award":["NSFC 82403766"],"award-info":[{"award-number":["NSFC 82403766"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,5,11]]},"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>While immune checkpoint inhibitor (ICI)-based therapy has shown promising efficacy in patients with metastatic non-clear cell renal cell carcinoma (nccRCC) in the first-line setting, the optimal treatment following disease progression remains undefined. We aimed to investigate the efficacy, safety, and predictive markers of ICI rechallenge in this population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>39 patients with metastatic nccRCC who received ICI rechallenge were enrolled. Key outcomes included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival. Whole exome sequencing, bulk RNA sequencing, and multiplex immunofluorescence (mIF) were performed to further explore potential biomarkers associated with the efficacy of ICI-rechallenge among nccRCC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Following ICI-rechallenge, the cohort demonstrated a median PFS of 11.8 months, an ORR of 13.9% and a DCR of 69.4%. Among clinicopathological variables, the fumarate hydratase-deficient renal cell carcinoma subtype was the only factor associated with the potential clinical benefit from ICI-rechallenge. Transcriptomic analysis revealed that an enrichment of B cells and central memory T cell signatures was associated with longer PFS (21.3 vs 7.9 months). Notably, patients with a higher mature intratumoral tertiary lymphoid structure (m-iTLS) score assessed by mIF showed higher ORR (50.0% vs 0.0%) and longer PFS (28.2 vs 5.0 months) compared with those with a lower m-iTLS score. In terms of safety, ICI rechallenge was generally well tolerated, with no accumulation or treatment-related deaths observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>ICI rechallenge may offer favorable clinical benefit and acceptable safety in patients with metastatic nccRCC. Higher density of mature iTLSs correlated with the efficacy of ICI-rechallenge but warrants further validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-013526","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T13:50:11Z","timestamp":1779976211000},"page":"e013526","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Pretreatment intratumoral mature TLSs in non-clear cell renal cell carcinoma are associated with response to immunotherapy rechallenge"],"prefix":"10.1136","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3369-5917","authenticated-orcid":false,"given":"Yanfeng","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Urology, West China Hospital of Sichuan University, Chengdu, Sichuan, 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