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Updated: Dec 22, 2025
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Angiogenic and immunomodulatory biomarkers in axitinib-treated patients with advanced renal cell carcinoma
Danielle A Murphy1, Brian I Rini2, Bernard Escudier3
1Pfizer Oncology, San Diego, CA 92121, USA.
Abstract:
Aim: Immunomodulatory mechanisms contributing to angiogenic inhibition in renal tumors are not well characterized. We report associations between efficacy and tumor-associated immune cells and mRNA/miRNA expression in patients from AXIS. Materials & methods: Immunohistochemistry (n = 52) and mRNA/miRNA expression analyses (n = 72) were performed on tumor samples. Results: In axitinib-treated patients, higher CXCR4 and TLR3 expression, respectively, was associated with longer progression-free survival (hazard ratio; 95% CI: 0.3; 0.1-0.8 and 0.4; 0.2-0.9) and showed interaction with treatment (p = 0.029 and p < 0.001); lower CCR7 expression was associated with objective response (odds ratio: 0.1; 95% CI: 0.01-1.0) and longer overall survival (hazard ratio: 3.9; 95% CI: 1.4-10.3). Conclusion: CCR7, CXCR4 and TLR3 expression levels may be prognostic/predictive of clinical benefit with axitinib. Clinical trial identifier: ClinicalTrials.gov NCT00678392.
Insights
Immune cell markers CCR7, CXCR4, and TLR3 show potential as biomarkers for predicting treatment response and survival in patients with renal tumors receiving axitinib therapy.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Immunomodulatory mechanisms in renal tumors are not fully understood.
- Angiogenic inhibition is a key factor in renal tumor treatment.
Purpose of the Study:
- To investigate the association between tumor-associated immune cells, mRNA/miRNA expression, and axitinib efficacy in renal tumors.
- To identify potential biomarkers for predicting clinical benefit from axitinib treatment.
Main Methods:
- Immunohistochemistry and mRNA/miRNA expression analyses were performed on renal tumor samples from patients treated with axitinib.
- Statistical analyses, including hazard ratios and odds ratios, were used to assess associations between marker expression and clinical outcomes.
Main Results:
- Higher CXCR4 and TLR3 expression correlated with longer progression-free survival in axitinib-treated patients.
- Lower CCR7 expression was associated with objective response and longer overall survival.
- CXCR4, TLR3, and CCR7 expression showed significant interaction with axitinib treatment.
Conclusions:
- CCR7, CXCR4, and TLR3 expression levels may serve as prognostic and predictive biomarkers for clinical benefit in patients with renal tumors treated with axitinib.
- These findings contribute to understanding the immunomodulatory landscape of renal tumors and their response to targeted therapy.
