Work

Spatial Profiling and Prognostic Role of Tumor-Infiltrating CD8+ T and CD20+ B Cells in Metastatic Clear Cell Renal Cell Carcinoma Treated with Sequential Tyrosine Kinase Inhibitors and Nivolumab

Year: 2026

Type: article

Abstract: Background: Tumor-infiltrating lymphocytes (TILs) are known to influence disease progression and treatment response in clear cell renal cell carcinoma.This study aimed at evaluating the prognostic and predictive relevance of T and B cell infiltration patterns in patients with metastatic clear cell renal cell carcinoma (mRCC-cc) treated sequentially with tyrosine kinase inhibitors (TKIs) and the immune checkpoint inhibitor nivolumab.Methods: In this retrospective cohort study, immune cell densities (CD3+, CD8+ T cells and CD20+ B cells) were analyzed by immunohistochemistry and quantified using digital image analysis software QuPath in distinct tumor regions of primary tumor: tumor center (TC), inner margin (IM), outer margin (OM), and peritumoral (PT) region.Samples were obtained from 36 patients with mRCC-cc treated with TKIs in the first line and sequentially with nivolumab in the second or third-line setting.Associations between immune cell densities, clinicopathological features, and survival outcomes were assessed using univariable and multivariable Cox regression models.Progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were evaluated.Results: Densities of all immune cells were significantly higher in the OM and PT regions than in the TC and IM.Older age correlated with lower CD8+ T cell and CD20+ B cell densities, whereas higher tumor grade was associated with increased CD20+ B cell infiltration in IM.High CD20+ B cell density in IM and OM was significantly associated with shorter PFS during first-line TKI therapy (hazard ratio (HR) = 3.30, P = 0.015 and HR = 3.25, P = 0.016, respectively).In contrast, an intermediate CD8+ T cell density in the PT region was associated with longer PFS during sequential nivolumab treatment (HR = 0.26, P = 0.007).No significant associations between immune cell densities and ORR or OS were observed.Conclusions: Our findings suggest that spatial localization and density of tumor-infiltrating CD20+ B cells are potential predictors of poor PFS on TKIs, whereas higher CD8+ T cell infiltration in peritumoral areas may be a potential predictor of prolonged PFS on nivolumab.These immune-cell-based parameters may refine prognostic models and help guide treatment selection in mRCC-cc.

Source: Journal of Cancer

DOI: 10.7150/jca.125509