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

Moran Gadot, Mordechay Gal, Paula Dobosz, Zohar Dotan, Jacob Ramon, Raanan Berger, Dror Avni, Eduard Fridman, Raya Leibowitz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)160-168
Number of pages9
JournalClinical and Experimental Immunology
Issue number2
StatePublished - Aug 2021


FundersFunder number
Israel Cancer Association


    • RCC
    • TCR
    • TIL
    • clonality
    • repertoire


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