Clin Exp Immunol. 2021 Apr 26. doi: 10.1111/cei.13608. Online ahead of print.
ABSTRACT
Renal cell carcinoma (RCC) comprises 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 PCR assay exclusively targets rearranged T-cell receptor (TCR) genes to generate high-throughput sequencing-based data, thus allowing to characterize the immune repertoire within tumors. Here we performed a retrospective analysis on archived tumor samples from patients with recurring vs non-recurring T3 ccRCC and on samples from early nccRCC vs 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 rho, respectively. Average fraction and clonality of T cells in tumors from non-recurring patients was 2.5-fold 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 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.
PMID:33899933 | DOI:10.1111/cei.13608
