2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T5f5,Aberrant alternative splicing (AS) events have been implicated in cancer progression; however, their role in metastatic renal cell carcinoma (mRCC) remains underexplored. This study aims to identify AS events associated with clinical benefits from immune checkpoint inhibitors and targeted therapies in mRCC. We conducted a retrospective analysis on 101 patients with mRCC who received systemic therapy and underwent RNA sequencing. Patients were divided into subgroups based on ICIs (alone or in combination) and targeted therapies. Responders and non-responders were classified according to Response Evaluation Criteria in Solid Tumors V.1.1 criteria. Differential gene expression and splicing analyses were performed between responders and non-responders in each cohort. Novel AS events were analyzed for their potential to generate peptide neoantigens through major histocompatibility complex (MHC) class I binding predictions. Outlier splicing analysis identified 10 aberrant splice events specific to mRCC. AS analysis revealed 461 differentially spliced events between responders and non-responders in the ICI cohort and 253 in the targeted therapy cohort, with intron retention as the predominant motif. Thirteen unique AS events were enriched in responders, including This study provides a comprehensive analysis of AS events in mRCC, highlighting intron retention as potential biomarkers for treatment response. Identified AS-derived neoantigens may serve as potential targets for adoptive cell therapy strategies.31:Tab4, Purpose Aberrant alternative splicing (AS) events have been implicated in cancer progression; however, their role in metastatic renal cell carcinoma (mRCC) remains underexplored. This study aims to identify AS events associated with clinical benefits from immune checkpoint inhibitors and targeted therapies in mRCC. Materials and methods We conducted a retrospective analysis on 101 patients with mRCC who received systemic therapy and underwent RNA sequencing. Patients were divided into subgroups based on ICIs (alone or in combination) and targeted therapies. Responders and non-responders were classified according to Response Evaluation Criteria in Solid Tumors V.1.1 criteria. Differential gene expression and splicing analyses were performed between responders and non-responders in each cohort. Novel AS events were analyzed for their potential to generate peptide neoantigens through major histocompatibility complex (MHC) class I binding predictions. Results Outlier splicing analysis identified 10 aberrant splice events specific to mRCC. AS analysis revealed 461 differentially spliced events between responders and non-responders in the ICI cohort and 253 in the targeted therapy cohort, with intron retention as the predominant motif. Thirteen unique AS events were enriched in responders, including PTPN6 and ACTN1 . Predictive neoantigen analysis identified high MHC class I binding potential in peptides from AS events in IFFO1 and ZNF692 . High splice burden was linked to an immunogenic tumor microenvironment, characterized by enriched antigen processing and adaptive immune responses. Conclusions This study provides a comprehensive analysis of AS events in mRCC, highlighting intron retention as potential biomarkers for treatment response. Identified AS-derived neoantigens may serve as potential targets for adoptive cell therapy strategies. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Metastatic Renal Cell Carcinoma: condition Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Metastatic Renal Cell Carcinoma (condition). Clinician-written summaries and actionable practice insights. 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These findings may eventually support hypoxia biomarker stratification when selecting between VEGFR-TKI/aPD-1 vs. dual checkpoint (aPD-1/anti-CTLA-4) regimens."}},{"doi":"10.1136/jitc-2025-012427","pmid":"42086309","title":"Characterization of aberrant alternative splicing landscape in patients with metastatic renal cell carcinoma","journal_title":"Journal for ImmunoTherapy of Cancer","journal_issn":"2051-1426","published_at":"2026-05-06T00:00:00.000Z","url":"https://doi.org/10.1136/jitc-2025-012427","source_score":44,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-05-05","doi":"10.1136/jitc-2025-012427","days":"14","issn":"2051-1426","rank":"5","field":"Clinical Medicine","score":"44","category":"Immunology","categories":["Immunology"],"_categories":["Immunology"]},"pubmed":{"doi":"10.1136/jitc-2025-012427","title":"Characterization of aberrant alternative splicing landscape in patients with metastatic renal cell carcinoma.","journal":"Journal for immunotherapy of cancer","methods":"","results":"Outlier splicing analysis identified 10 aberrant splice events specific to mRCC. 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Thirteen AS events were enriched in responders (including PTPN6 and ACTN1), and high splice burden correlated with an immunogenic tumor microenvironment. IFFO1 and ZNF692 AS-derived peptides showed high MHC class I binding potential as candidate neoantigens.","limitations":"Retrospective single-cohort design limits causal inference and generalizability. Sample size (n=101) may be underpowered for subgroup analyses. Neoantigen binding predictions are computational only — no functional or clinical validation of AS-derived neoantigens is reported.","practice_takeaway":"Intron retention events may emerge as RNA-based biomarkers for ICI response in mRCC. AS-derived neoantigens from IFFO1 and ZNF692 are early-stage candidates worth exploring in adoptive cell therapy trials, but require prospective validation before clinical use."}}],"initialOffset":2,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"condition","value":"Metastatic Renal Cell Carcinoma"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Conditions","href":"/hub/tag/condition"},{"name":"Metastatic Renal Cell Carcinoma"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"condition","hub_tag_value":"Metastatic Renal Cell Carcinoma"}}}]]

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