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

Rákkutatás · Hepatocellular carcinoma

Progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were evaluated.

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. 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. Keywords: metastatic renal cell carcinoma, progression-free survival, tyrosine kinase inhibitors, immune checkpoint inhibitors, tumor-infiltrating lymphocytes

Elevated immune cell densities, especially of CD20+ B cells, are associated with poor progression-free survival under TKI therapy in metastatic clear cell renal cell carcinoma, whereas higher CD8+ T cell infiltration in peritumoral zones predicts prolonged PFS with nivolumab. The prognostic implications of these spatial distribution patterns may aid in refining therapeutic decisions and selecting patients most likely to benefit from specific anti‑VEGF or immune checkpoint strategies.

Bizonyítékszint: Klinikai vizsgálat. Formális klinikai vizsgálati eredmény.

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