Associations between T cell infiltration, T cell receptor clonality, histology and recurrence in renal cell carcinoma

Summary 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.