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

Autor:	Raya Leibowitz, Zohar A. Dotan, Jacob Ramon, Dror Avni, Eduard Fridman, Mordechay Gal, Paula Dobosz, Moran Gadot, Raanan Berger
Rok vydání:	2021
Předmět:	Male 0301 basic medicine T-Lymphocytes T cell Immunology Receptors Antigen T-Cell Biology 03 medical and health sciences 0302 clinical medicine Renal cell carcinoma Multiplex polymerase chain reaction medicine Humans Immunology and Allergy Receptor Carcinoma Renal Cell Retrospective Studies T-cell receptor Histology Middle Aged medicine.disease Kidney Neoplasms genomic DNA 030104 developmental biology medicine.anatomical_structure Localized disease Cancer research Female ORIGINAL ARTICLES Neoplasm Recurrence Local 030215 immunology
Zdroj:	Clin Exp Immunol
ISSN:	1365-2249 0009-9104
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6f87b349762838ffbb7e4ee08561c0db https://doi.org/10.1111/cei.13608 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.