Can histopathology help predict response to immunotherapy in metastatic clear cell renal cell carcinoma (mccRCC)? A new retrospective study presented at ASCO 2025 suggests that TILplus—a simple scoring system based on immune infiltrate proximity in H&E-stained metastatic tissue—may serve as a valuable biomarker. Here’s an in-depth look at the study and its findings.
TILplus Score as a Potential Predictive Biomarker in First-Line ICI Therapy for mccRCC
05/30/2025
Choose a format
The treatment landscape for metastatic clear cell renal cell carcinoma (mccRCC) has increasingly incorporated immune checkpoint inhibitor (ICI)-based regimens as the standard of care in the first-line setting. However, robust biomarkers to predict treatment outcomes with these therapies remain lacking.
In a recent retrospective analysis presented at ASCO 2025, Ged and team explored the prognostic value of histopathologic markers—TILplus and necrosis—in the context of first-line ICI combinations.
Study Design and Biomarker Assessment
This retrospective study included 35 patients with histologically-confirmed mccRCC treated at a single institution between 2013 and 2024. All patients received first-line ICI therapy, either as dual ICI combinations or ICI plus a tyrosine kinase inhibitor (TKI). Eligibility also required availability of hematoxylin and eosin (H&E)-stained slides from metastatic lesions prior to treatment (excluding brain metastases).
Using previously published methods, researchers scored TILplus as follows:
- TILplus 1: Immune cell infiltrate interfacing with tumor
- TILplus 0: No immune infiltrate identified involving tumor
Necrosis was scored independently, based on surface area involvement (>10 percent = score 1; ≤10 percent = score 0).
Survival Outcomes and Biomarker Associations
Patients with tumors that had a TILplus score of 1 experienced significantly improved outcomes:
- Median Overall Survival (OS):Not reached (TILplus 1) versus 24.0 months (TILplus 0); p = 0.04
- Median Progression-Free Survival (PFS):23.7 months versus 9.9 months; p = 0.01
By contrast, necrosis scores did not show any association with OS or PFS. These findings were observed across both ICI-only and ICI+TKI treatment groups.
Clinical Implications and Future Directions
This study suggests that TILplus , a binary scoring system for tumor histopathology based on routine H&E staining, may have value as a predictive biomarker for clinical response to first-line ICI-based therapies in mccRCC. While promising, the retrospective nature of the analysis underscores the need for prospective clinical validation before TILplus can be integrated into routine practice or used to guide therapeutic decisions.
Reference:
Ged Y, Baraban E, Feinaj A, Singla N, Deutsch J. Baseline histopathologic biomarker for predicting frontline immunotherapy combination outcomes in metastatic clear cell renal cell carcinoma (mccRCC). J Clin Oncol. 2025;43(16_suppl):e16539. doi:10.1200/JCO.2025.43.16_suppl.e16539
Details