Associations between T cell infiltration, T cell receptor clonality, histology and recurrence in renal cell carcinoma,Clinical & Experimental Immunology

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Associations between T cell infiltration, T cell receptor clonality, histology and recurrence in renal cell carcinoma
Clinical & Experimental Immunology ( IF 3.4 ) Pub Date : 2021-04-26 , DOI: 10.1111/cei.13608
Moran Gadot ₁ , Mordechay Gal ₂ , Paula Dobosz ₃ , Zohar Dotan _{4,

5} , Jacob Ramon _{4,

5} , Raanan Berger _{1,

5} , Dror Avni _{5,

6} , Eduard Fridman _{5,

7} , Raya Leibowitz _{5,

8}

Affiliation

Renal cell carcinoma (RCC) is comprised of clear-cell (ccRCC) and non-clear-cell (nccRCC) tumors. Despite definitive surgical resection in localized disease, recurrence often occurs. A commercial method based on a multiplex polymerase chain reaction (PCR) assay exclusively targets rearranged T cell receptor (TCR) genes to generate high-throughput sequencing-based data, allowing characterization of the immune repertoire within tumors. In this study we performed a retrospective analysis on archived tumor samples from patients with recurring versus non-recurring T3 ccRCC and on samples from early nccRCC versus ccRCC. Following genomic DNA extraction and multiplex PCR, the fraction of T cells within tumors, the number of unique receptors (‘richness’) and their relative abundances (‘clonality’) were calculated. Statistical significance and correlations were calculated using Student’s t-test and Spearman’s rho, respectively. Average fraction and clonality of T cells in tumors from non-recurring patients was 2.5- and 4.3-fold higher than in recurring patients (P = 0.025 and P = 0.043, respectively). A significant positive correlation was found between T cell fraction and clonality (Spearman’s rho = 0.78, P = 0.008). The average fraction of T cells in ccRCC tumors was 2.8-fold higher than in nccRCC tumors (P = 0.015). Clonality and estimated richness were similar between ccRCC and nccRCC tumors. In summary, recurrence of ccRCC is associated with a lower fraction and clonality of T cells within tumors; nccRCC tumors are more ‘deserted’ than ccRCC, but similar in their ability to generate a clonal T cell repertoire. Our work suggests associations between the characteristics of T cell infiltrate, histology and tumor recurrence.

中文翻译：

T细胞浸润、T细胞受体克隆性、组织学和肾细胞癌复发之间的关联

肾细胞癌 (RCC) 由透明细胞 (ccRCC) 和非透明细胞 (nccRCC) 肿瘤组成。尽管对局部疾病进行了明确的手术切除，但经常会发生复发。一种基于多重聚合酶链反应 (PCR) 测定的商业方法专门针对重排的 T 细胞受体 (TCR) 基因，以生成基于高通量测序的数据，从而可以表征肿瘤内的免疫库。在这项研究中，我们对来自复发性与非复发性 T3 ccRCC患者的存档肿瘤样本以及早期 nccRCC与ccRCC。在基因组 DNA 提取和多重 PCR 之后，计算肿瘤内 T 细胞的比例、独特受体的数量（“丰富度”）及其相对丰度（“克隆性”）。分别使用学生t检验和斯皮尔曼 rho计算统计显着性和相关性。非复发患者肿瘤中 T 细胞的平均分数和克隆性比复发患者高 2.5 倍和 4.3 倍（分别为P = 0.025 和P = 0.043）。在 T 细胞分数和克隆性之间发现了显着的正相关（Spearman 的 rho = 0.78，P = 0.008）。ccRCC 肿瘤中 T 细胞的平均比例是 nccRCC 肿瘤的 2.8 倍（P = 0.015)。ccRCC 和 nccRCC 肿瘤的克隆性和估计丰富度相似。总之，ccRCC 的复发与肿瘤内 T 细胞的较低比例和克隆性有关。nccRCC 肿瘤比 ccRCC 更“荒芜”，但它们产生克隆 T 细胞库的能力相似。我们的工作表明 T 细胞浸润的特征、组织学和肿瘤复发之间存在关联。

更新日期：2021-04-26

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