CXCR3 Expression Is Associated with Advanced Tumor Stage and Grade Influencing Survival after Surgery of Localised Renal Cell Carcinoma.

Background: Surgery is the standard treatment in localized renal cell carcinoma (RCC). Pembrolizumab is now approved for adjuvant therapy in high-risk patients. However, inhomogeneity of studies gives ambiguity which patient benefit most from adjuvant therapy. A high infiltration of CD8 ⁺ T cells is known to be linked with poor prognosis in RCC. CXCR3 is a key player of CD8 ⁺ T cell differentiation and infiltration. We aimed to evaluate CXCR3 as a potential marker for predicting recurrence.
Methods: CXCR3 and immune cell subsets (CD4, CD8, CD68 and FoXP3) were measured on RCC samples by multiplex immunofluorescence (mIF) staining. Cellular localization of CXCR3 was evaluated using single-cell RNA analysis on a publicly available dataset.
Results: Tumor samples of 42 RCC patients were analyzed, from which 59.5% were classified as clear-cell RCC and of which 20 had recurrence. Single-cell RNA analysis revealed that CXCR3 was predominantly expressed in intratumoral T cells and dendritic cells. CXCR3 expression was higher in advanced tumors stages ( p = 0.0044) and grade ( p = 0.0518), correlating significantly with a higher CD8 ⁺ T cell expression ( p < 0.001). Patients with CXCR3 ^high RCCs had also a significant shorter RFS compared to CXCR3 ^low (median: 78 vs. 147 months, p = 0.0213). In addition, also tumor stage pT3/4 ( p < 0.0001) as well as grade G3/4 ( p = 0.0008) negatively influenced RFS.
Conclusion: CXCR3 ^high cell density was associated with high T cell infiltration and advanced tumor stage, worsening RFS in surgically resected RCC patients. Beside its prognostic value, CXCR3 might be a predictive biomarker to guide therapy decision for adjuvant therapy in localized RCC.