ArticleClinical cancer research : an official journal of the American Association for Cancer Research2024
KIR2DL2/DL3+NKs and Helios+Tregs in Peripheral Blood Predict Nivolumab Response in Patients with Metastatic Renal Cell Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Peripheral blood biomarkers for predicting response to PD-1/PD-L1 inhibitors.Biomarker research · 2026Review
- Regulatory T cells in breast cancer drivers of immune suppression and targets for immunotherapy.Frontiers in immunology · 2026Review
- Multimodal risk profiles reveal shared and disease-specific risks of major non-communicable diseases: a prospective cohort study of 42,666 individuals.International journal of public health · 2026Article
- Charting the immune terrain: a novel risk model for thyroid cancer prognosis.Frontiers in genetics · 2026Article
- PILRA serves as a diagnostic and prognostic biomarker and modulates the tumor immune microenvironment and immunotherapy response in breast cancer.Frontiers in immunology · 2025Article
- Identification and validation the predictive biomarkers based on risk-adjusted control chart in gemcitabine with or without erlotinib for pancreatic cancer therapy.Frontiers in genetics · 2024Article
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24 authors.
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Abstract
purposeTo identify predictive factors of nivolumab sensitivity, peripheral blood NKs and regulatory T-cell (Treg) were evaluated in patients with metastatic renal cell carcinoma (mRCC) enrolled in the REVOLUTION trial. EXPERIMENTAL
designFifty-seven mRCCs being treated with nivolumab, as at least second-line of therapy, and 62 healthy donors were longitudinally evaluated (0-1-3-6-12 months) for peripheral NKs and Tregs, phenotype, and function. Multivariable logistic regression was conducted to identify the independent predictors. The 0.632+ internal cross-validation was used to avoid overfitting. The best cutoff value based on a 3-month clinical response was applied to progression-free survival (PFS) and overall survival (OS). Kaplan-Meier curves for PFS and OS were produced.
resultsAt pretreatment, mRCCs displayed high frequency of NKp46+NKs, NKp30+NKs, KIR2DL1+NKs, KIR2DL2/DL3+NKs, and PD1+NKs with reduced NK degranulation as well as high frequency of Tregs, PD1+Tregs, Helios+Tregs, and ENTPD1+Tregs. Responder patients, identified as a clinical response after 3 months of treatment, presented at pretreatment significantly low CD3+, high KIR2DL2/DL3+NKs, high PD1+Tregs, and high Helios+Tregs. Upon multivariate analysis, only KIR2DL2/DL3NKs and Helios+Tregs held as independent predictors of nivolumab responsiveness. The KIR2DL2/DL3+NKs >35.3% identified patients with longer OS, whereas the Helios+Tregs >34.3% displayed significantly longer PFS. After 1-month of nivolumab, responder patients showed low CD3+, high NKs, KIR2DL2/DL3+NKs, and ICOS+Tregs. Among these subpopulations, CD3+ and KIR2DL2/DL3+NKs held as independent predictors of nivolumab efficacy. Low CD3+ (≤71%) was significantly associated with longer PFS, whereas high KIR2DL2/DL3+NKs (>23.3%) were associated with both PFS and OS.
conclusionsPretreatment evaluation of Helios+Tregs/KIR2DL2/DL3+NKs and 1-month posttreatment CD3+/ KIR2DL2/DL3+NKs will predict nivolumab response in mRCCs.
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