TIL^plus Score as a Potential Predictive Biomarker in First-Line ICI Therapy for mccRCC

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—TIL^plus 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 TIL^plus as follows:

• TIL^plus 1: Immune cell infiltrate interfacing with tumor
• TIL^plus 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 TIL^plus score of 1 experienced significantly improved outcomes:

• Median Overall Survival (OS):Not reached (TIL^plus 1) versus 24.0 months (TIL^plus 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 TIL^plus , 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 TIL^plus 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