Lindner Andrea Katharina, Martowicz Agnieszka, Untergasser Gerold, Haybaeck Johannes, Compérat Eva, Kocher Florian, Seeber Andreas, Thurnher Martin, Pichler Renate
Department of Urology, Comprehensive Cancer Center Innsbruck (CCCI), Medical University Innsbruck, 6020 Innsbruck, Austria.
Tyrolpath Obrist Brunhuber GmbH, 6511 Zams, Austria.
Cancers (Basel). 2023 Feb 4;15(4):1001. doi: 10.3390/cancers15041001.
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.
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.
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 was predominantly expressed in intratumoral T cells and dendritic cells. CXCR3 expression was higher in advanced tumors stages ( = 0.0044) and grade ( = 0.0518), correlating significantly with a higher CD8 T cell expression ( < 0.001). Patients with CXCR3 RCCs had also a significant shorter RFS compared to CXCR3 (median: 78 vs. 147 months, = 0.0213). In addition, also tumor stage pT3/4 ( < 0.0001) as well as grade G3/4 ( = 0.0008) negatively influenced RFS.
CXCR3 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.
手术是局限性肾细胞癌（RCC）的标准治疗方法。帕博利珠单抗现已被批准用于高危患者的辅助治疗。然而，研究的异质性使得对于哪些患者从辅助治疗中获益最大存在模糊性。已知CD8 T细胞的高浸润与RCC的不良预后相关。CXCR3是CD8 T细胞分化和浸润的关键因素。我们旨在评估CXCR3作为预测复发的潜在标志物。
通过多重免疫荧光（mIF）染色在RCC样本上检测CXCR3和免疫细胞亚群（CD4、CD8、CD68和FoxP3）。使用公开可用数据集中的单细胞RNA分析评估CXCR3的细胞定位。
分析了42例RCC患者的肿瘤样本，其中59.5%被分类为透明细胞RCC，其中20例复发。单细胞RNA分析显示CXCR3主要在肿瘤内T细胞和树突状细胞中表达。CXCR3表达在晚期肿瘤阶段（P = 0.0044）和分级（P = 0.0518）中较高，与较高的CD8 T细胞表达显著相关（P < 0.001）。与CXCR3低表达的RCC患者相比，CXCR3高表达的患者无复发生存期（RFS）也显著缩短（中位数：78个月对147个月，P = 0.0213）。此外，肿瘤分期pT3/4（P < 0.0001）以及分级G3/4（P = 0.0008）也对RFS产生负面影响。
CXCR3细胞密度与高T细胞浸润和晚期肿瘤阶段相关，使手术切除的RCC患者的RFS恶化。除了其预后价值外，CXCR3可能是指导局限性RCC辅助治疗决策的预测生物标志物。
