@article{c91138d142d34b39bcdd7ab4d6796a48,
title = "Associations between T cell infiltration, T cell receptor clonality, histology and recurrence in renal cell carcinoma",
abstract = "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 ({\textquoteleft}richness{\textquoteright}) and their relative abundances ({\textquoteleft}clonality{\textquoteright}) were calculated. Statistical significance and correlations were calculated using Student{\textquoteright}s t-test and Spearman{\textquoteright}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{\textquoteright}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 {\textquoteleft}deserted{\textquoteright} 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.",
keywords = "RCC, TCR, TIL, clonality, repertoire",
author = "Moran Gadot and Mordechay Gal and Paula Dobosz and Zohar Dotan and Jacob Ramon and Raanan Berger and Dror Avni and Eduard Fridman and Raya Leibowitz",
note = "Publisher Copyright: {\textcopyright} 2021 British Society for Immunology",
year = "2021",
month = aug,
doi = "10.1111/cei.13608",
language = "אנגלית",
volume = "205",
pages = "160--168",
journal = "Clinical and Experimental Immunology",
issn = "0009-9104",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "2",
}