Predicting which patients will progress to metastatic disease after surgery for non-metastatic clear cell renal cell carcinoma (ccRCC) is difficult; however, recent data suggest that tumor immune cell infiltration could be used as a biomarker. We evaluated the quantity and type of immune cells infiltrating ccRCC tumors for associations with metastatic progression following attempted curative surgery. We quantified immune cell densities in the tumor microenvironment and validated our findings in two independent patient cohorts with multi-region sampling to investigate the impact of heterogeneity on prognostic accuracy. For non-metastatic ccRCC, increased CD8+T cell infiltration was associated with a reduced likelihood of progression to metastatic disease. Interestingly, patients who progressed to metastatic disease also had increased percentages of exhausted CD8+T cells. Finally, we evaluated the spatial heterogeneity of the immune infiltration and demonstrated that patients without metastatic progression had CD8+T cells in closer proximity to ccRCC cells. These data strengthen the evidence for CD8+T cell infiltration as a prognostic biomarker in non-metastatic ccRCC and demonstrate that multi-region sampling may be necessary to fully characterize immune infiltration within heterogeneous tumors. Tumor CD8+T cell infiltration should be investigated as a biomarker in adjuvant systemic therapy clinical trials for high-risk non-metastatic RCC.
预测哪些非转移性透明细胞肾细胞癌（ccRCC）患者在手术后会进展为转移性疾病较为困难；然而，近期研究表明肿瘤免疫细胞浸润可作为生物标志物。我们评估了ccRCC肿瘤中浸润免疫细胞的数量和类型，以探究其与根治性手术后转移进展的关联。通过量化肿瘤微环境中的免疫细胞密度，并在两个采用多区域采样的独立患者队列中验证结果，我们研究了肿瘤异质性对预后准确性的影响。对于非转移性ccRCC，CD8+T细胞浸润增加与转移进展风险降低相关。值得注意的是，进展为转移性疾病的患者中耗竭型CD8+T细胞比例也显著升高。最后，我们评估了免疫浸润的空间异质性，发现未发生转移进展的患者其CD8+T细胞与ccRCC细胞的空间距离更近。这些数据强化了CD8+T细胞浸润作为非转移性ccRCC预后生物标志物的证据，并表明多区域采样可能是全面表征异质性肿瘤内免疫浸润特征的必要手段。在高危非转移性肾细胞癌的辅助全身治疗临床试验中，应进一步研究肿瘤CD8+T细胞浸润作为生物标志物的价值。
肿瘤(癌症)患者之家