Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Aug;205(2):160-168.
doi: 10.1111/cei.13608. Epub 2021 Jun 2.

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

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
Affiliations

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

Moran Gadot et al. Clin Exp Immunol. 2021 Aug.

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 ('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.

Keywords: RCC; TCR; TIL; clonality; repertoire.

PubMed Disclaimer

Conflict of interest statement

None of the authors have any relevant potential conflicts of interest.

Figures

FIGURE 1
FIGURE 1
(a) Kaplan–Meier curve of recurring and non‐recurring patients using the log‐rank test (P = 0.022). (b) Fraction of T cells in individual patients with non‐recurring (black) and recurring (gray) T3 clear‐cell renal cell carcinoma (ccRCC). (c) T cell receptor (TCR) clonality in non‐recurring (black) and recurring (gray) T3 ccRCC. (d) TCR richness in non‐recurring (black) and recurring (gray) T3 ccRCC. The horizontal line represents the average for each population
FIGURE 2
FIGURE 2
(a) Graphic depiction of clonality (y‐axis) versus fraction (x‐axis) in 10 T3 clear‐cell renal cell carcinoma (ccRCC). Black dots = non‐recurring tumors; gray dots = recurring tumors. (b) Graphic depiction of time to recurrence (in months, y‐axis) versus fraction (x‐axis) in seven recurring T3 ccRCC
FIGURE 3
FIGURE 3
T cell fraction (a), Clonality (b) and richness (c) in nine individual clear‐cell (black), two papillary (dark gray) and four chromophobe (light gray) renal tumors. The horizontal line represents the average for each population
FIGURE 4
FIGURE 4
A cartoon depicting the proposed model of T cell infiltration in non‐recurring and recurring tumors. The green circles represent T cells within the kidney tumor, and different T cell receptor (TCR) clonalities are depicted as different colors of transmembrane proteins
See this image and copyright information in PMC

References

    1. Moch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM. The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs – part A: renal, penile, and testicular tumours. Eur Urol. 2016;70:93–105. doi:10.1016/j.eururo.2016.02.029 - DOI - PubMed
    1. Leibovich BC, Lohse CM, Cheville JC, Zaid HB, Boorjian SA, Frank I, et al. Predicting oncologic outcomes in renal cell carcinoma after surgery. Eur Urol. 2018;73:772–80. doi:10.1016/j.eururo.2018.01.005 - DOI - PubMed
    1. Gul A, Rini BI. Adjuvant therapy in renal cell carcinoma. Cancer 2019;125:2935–44. doi:10.1002/cncr.32144 - DOI - PubMed
    1. Siddiqui SA, Frank I, Leibovich BC, Cheville JC, Lohse CM, Zincke H, et al. Impact of tumor size on the predictive ability of the pT3a primary tumor classification for renal cell carcinoma. J Urol. 2007;177:59–62. doi:10.1016/j.juro.2006.08.069 - DOI - PubMed
    1. Delahunt B, Eble JN, Egevad L, Samaratunga H. Grading of renal cell carcinoma. Histopathology 2019;74:4–17. doi:10.1111/his.13735 - DOI - PubMed

Publication types

Substances