Radiation induces dynamic changes to the T cell repertoire in renal cell carcinoma patients

Strong evidence supports the tumor immune landscape as a determinant of patient responses to immunotherapy. Readily available therapies, including radiation, are being investigated as modifying agents with immune checkpoint blockade. However, surprisingly little is known regarding radiotherapy's impact within the tumor microenvironment and intratumoral T cell repertoires of patients, leaving critical gaps to guided design of clinical protocols. Here, samples from renal cell carcinoma (RCC) patients underwent high-throughput analysis to reveal transcriptional immune activation and increased clonality in irradiated tumors. Overall design: Comparing transcriptomes of treatment-naïve, resected patient primary renal cell carcinoma (RCC) tumors versus patient primary RCC tumors treated with 1 x 15 Gy radiation by SBRT, followed by nephrectomy at 4 weeks post radiation.

已有大量证据证实，肿瘤免疫图谱（tumor immune landscape）是决定患者免疫治疗应答效果的核心因素。当前学界正探索包括放疗在内的可及性治疗手段，将其作为联合免疫检查点阻断治疗的免疫调节辅助手段。然而，令人意外的是，目前对放疗在患者肿瘤微环境（tumor microenvironment）及肿瘤内T细胞库（intratumoral T cell repertoires）中产生的影响仍知之甚少，这为临床方案的精准设计留下了关键空白。
本研究对肾细胞癌（renal cell carcinoma, RCC）患者的样本开展高通量分析，揭示了受照射肿瘤中存在转录层面的免疫激活特征与克隆性升高的现象。
总体研究设计：对比未经术前治疗、已手术切除的原发性肾细胞癌（RCC）患者肿瘤样本，与接受1次15 Gy立体定向体部放疗（SBRT）、并于放疗后4周接受肾切除术的原发性RCC患者肿瘤样本的转录组差异。