Abstract
To 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. Fifty-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. At 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. Pretreatment evaluation of Helios+Tregs/KIR2DL2/DL3+NKs and 1-month posttreatment CD3+/ KIR2DL2/DL3+NKs will predict nivolumab response in mRCCs.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Clinical cancer research : an official journal of the American Association for Cancer Research
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
