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Soluble Immune Checkpoint Molecules as Predictors of Efficacy in Immuno-Oncology Combination Therapy in Advanced
Kosuke Ueda1, Keiichiro Uemura1, Naoki Ito1
1Department of Urology, Kurume University School of Medicine, Kurume 830-0011, Japan.
Abstract:
Immuno-oncology (IO) combination therapy is the first-line treatment for advanced renal cell carcinoma (RCC). However, biomarkers for predicting the response to IO combination therapy are lacking. Here, we investigated the association between the expression of soluble immune checkpoint molecules and the therapeutic efficacy of IO combination therapy in advanced RCC. The expression of soluble programmed cell death-1 (sPD-1), soluble programmed cell death ligand-1 (sPD-L1), soluble PD-L2 (sPD-L2), and lymphocyte activation gene-3 (sLAG-3) was assessed in plasma samples from 42 patients with advanced RCC who received first-line IO combination therapy. All IMDC risk classifications were represented among the patients, including 14.3, 57.1, and 28.6% with favorable, intermediate, and poor risk, respectively. Univariate analysis revealed that prior nephrectomy, sPD-L2 levels, and sLAG-3 levels were significant factors affecting progression-free survival (PFS), whereas multivariate analyses suggested that sPD-L2 and sLAG-3 levels were independent prognostic factors for PFS. In a univariate analysis of the overall survival, prior nephrectomy and sPD-L2 levels were significant factors; no significant differences were observed in the multivariate analysis. No significant correlation was observed between the sPD-L2 and sLAG-3 levels and PD-L2 and LAG-3 expression via immunohistochemistry. In conclusion, sPD-L2 and sLAG-3 expression may serve as a potential biomarker for predicting IO combination therapy efficacy.
Insights
Soluble programmed cell death ligand-1 (sPD-L2) and soluble lymphocyte activation gene-3 (sLAG-3) levels in plasma may predict treatment effectiveness for advanced renal cell carcinoma (RCC) patients receiving immuno-oncology combination therapy.
Area of Science:
- Oncology
- Immunology
- Biomarker Discovery
Background:
- Immuno-oncology (IO) combination therapy is a standard first-line treatment for advanced renal cell carcinoma (RCC).
- Predictive biomarkers for IO therapy response in advanced RCC are currently lacking.
- Understanding factors influencing treatment efficacy is crucial for optimizing patient outcomes.
Purpose of the Study:
- To investigate the association between soluble immune checkpoint molecule expression and therapeutic efficacy in advanced RCC patients undergoing first-line IO combination therapy.
- To identify potential plasma-based biomarkers for predicting response to IO therapy in advanced RCC.
- To evaluate the prognostic value of soluble programmed cell death ligand-1 (sPD-L2) and soluble lymphocyte activation gene-3 (sLAG-3) in advanced RCC.
Main Methods:
- Plasma samples from 42 advanced RCC patients receiving first-line IO combination therapy were analyzed.
- Expression levels of soluble programmed cell death-1 (sPD-1), soluble programmed cell death ligand-1 (sPD-L1), sPD-L2, and sLAG-3 were measured.
- Progression-free survival (PFS) and overall survival were assessed in relation to biomarker levels and clinical factors.
Main Results:
- Univariate analysis indicated that prior nephrectomy, sPD-L2, and sLAG-3 levels significantly impacted PFS.
- Multivariate analyses identified sPD-L2 and sLAG-3 levels as independent prognostic factors for PFS.
- No significant correlation was found between soluble marker levels and their corresponding immunohistochemically assessed protein expression in tumor tissue.
Conclusions:
- Soluble PD-L2 and sLAG-3 levels in plasma show potential as predictive biomarkers for the efficacy of first-line IO combination therapy in advanced RCC.
- These soluble markers may aid in patient selection and treatment strategy for advanced RCC.
- Further validation studies are warranted to confirm the clinical utility of sPD-L2 and sLAG-3 in advanced RCC.
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