ArticleCancer research and treatment2023
Favorable Immunotherapy Plus Tyrosine Kinase Inhibition Outcome of Renal Cell Carcinoma Patients with Low CDK5 Expression.
Article in Cancer research and treatment, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
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Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it, 6 citations in OpenAlex.
- A systematic review of the latest progress of drug resistance and clinical application of immunotherapy in renal cell carcinoma in the past five years based on bibliometrics.Human vaccines & immunotherapeutics · 2025Pooled it
- SPP1 expression indicates outcome of immunotherapy plus tyrosine kinase inhibition in advanced renal cell carcinoma.Human vaccines & immunotherapeutics · 2024Article
- PSMD2 overexpression as a biomarker for resistance and prognosis in renal cell carcinoma treated with immune checkpoint and tyrosine kinase inhibitors.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Efficacy and Safety of Immuno-Oncology Plus Tyrosine Kinase Inhibitors as Late-Line Combination Therapy for Patients with Advanced Renal Cell Carcinoma.Journal of clinical medicine · 2024Article
- Effectiveness of switch therapy from tyrosine kinase inhibitors to immune checkpoint inhibitors: the need for biomarkers to establish treatment strategies in patients with metastatic renal cell carcinoma.Translational andrology and urology · 2024Article
- External validation of hemoglobin and neutrophil levels as predictors of the effectiveness of ipilimumab plus nivolumab for treating renal cell carcinoma.Frontiers in oncology · 2024Article
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
purposeImmunotherapy (IO) plus tyrosine kinase inhibitor (TKI) has become the first-line treatment for advanced renal cell carcinoma, despite the lack of prognostic biomarkers. Cyclin-dependent kinase 5 (CDK5) affects the tumor microenvironment, which may influence the efficacy of TKI+IO. MATERIALS AND
methodsTwo cohorts from our center (Zhongshan Metastatic Renal Cell Carcinoma [ZS-MRCC] cohort, Zhongshan High-risk Localized Renal Cell Carcinoma [ZS-HRRCC] cohort) and one cohort from a clinical trial (JAVELIN-101) were enrolled. The expression of CDK5 of each sample was determined by RNA sequencing. Immune infiltration and T cell function were evaluated by flow cytometry and immunohistochemistry. Response and progression-free survival (PFS) were set as primary endpoints.
resultsPatients of low CDK5 expression showed higher objective response rate (60.0% vs. 23.3%) and longer PFS in both cohorts (ZS-MRCC cohort, p=0.014; JAVELIN-101 cohort, p=0.040). CDK5 expression was enhanced in non-responders (p < 0.05). In the ZS-HRRCC cohort, CDK5 was associated with decreased tumor-infiltrating CD8+ T cells, which was proved by immunohistochemistry (p < 0.05) and flow cytometry (Spearman's ρ=-0.49, p < 0.001). In the high CDK5 subgroup, CD8+ T cells revealed a dysfunction phenotype with decreased granzyme B, and more regulatory T cells were identified. A predictive score was further constructed by random forest, involving CDK5 and T cell exhaustion features. The RFscore was also validated in both cohorts. By utilizing the model, more patients might be distinguished from the overall cohort. Additionally, only in the low RFscore did TKI+IO outperform TKI monotherapy.
conclusionHigh-CDK5 expression was associated with immunosuppression and TKI+IO resistance. RFscore based on CDK5 may be utilized as a biomarker to determine the optimal treatment strategy.
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