Immune biomarker evaluation of sequential tyrosine kinase inhibitor and nivolumab monotherapies in renal cell carcinoma: The phase 1 TRIBE trial
Immuno-Oncology and Technology(2024)
Abstract
Background
Predictive biomarkers for immune checkpoint blockade (ICB) in the second-line (2L) treatment of metastatic renal cell carcinoma (mRCC) are lacking.
Methods
Patients with histologically confirmed RCC who started nivolumab after at least four months of tyrosine kinase inhibitors (TKIs) were recruited for this study. Serial tissue and blood samples were collected for immune biomarker evaluation. The primary endpoint was to determine the association of specific T cell subsets with clinical outcomes tested using Wilcoxon rank sum for clinical benefit rate (CBR) and log-rank test for progression-free survival (PFS).
Results
Twenty patients were included in this trial with a median age of 64 years and followed-up for a median of 12 months. The median PFS for patients who received TKI was 13.8 months, while for those subsequently treated with nivolumab following TKI therapy, the median PFS was 2.6 months. CBR of nivolumab was 20% with two partial responses. Functionally active PD1+ CD4+ T cells were enriched in non-responders (q=0.003) and associated with worse PFS on nivolumab (p=0.04). Responders showed a significant reduction in the effector CD4+T cell (TEF) fraction compared to non-responders at 3 months on nivolumab (0.40 vs 0.80, p=0.0005). CD127+CD4+ T cells were enriched in patients who developed immune-related adverse effects (q=0.003). Using in-house validated multiplex immunohistochemistry for six markers, we measured tumour-associated immune cell densities in tissue samples. Responders to nivolumab showed a significantly higher mean of immune cell densities in tissue samples compared to non-responders (346 vs 87 cells/mm2, p= 0.04).
Conclusion
In this small study, analysis of tissue-based and peripheral blood immune cell subsets predicted clinical outcomes of nivolumab. Further studies are warranted with larger populations to validate these observations.
MoreTranslated text
Key words
Predictive biomarkers,immune checkpoint blockade,metastatic renal cell carcinoma,nivolumab,progression-free survival,clinical benefit rate
AI Read Science
Must-Reading Tree
Example
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined