T cell receptor gene repertoire profiles in subgroups of patients with chronic lymphocytic leukemia bearing distinct genomic aberrations.

Background

Microenvironmental interactions of the malignant clone with T cells are critical throughout the natural history of chronic lymphocytic leukemia (CLL). Indeed, clonal expansions of T cells and shared clonotypes exist between different CLL patients, strongly implying clonal selection by antigens. Moreover, immunogenic neoepitopes have been isolated from the clonotypic B cell receptor immunoglobulin sequences, offering a rationale for immunotherapeutic approaches. Here, we interrogated the T cell receptor (TR) gene repertoire of CLL patients with different genomic aberration profiles aiming to identify unique signatures that would point towards an additional source of immunogenic neoepitopes for T cells.

Experimental design

TR gene repertoire profiling using next generation sequencing in groups of patients with CLL carrying one of the following copy-number aberrations (CNAs): del(11q), del(17p), del(13q), trisomy 12, or gene mutations in

Results

Oligoclonal expansions were found in all patients with distinct recurrent genomic aberrations; these were more pronounced in cases bearing CNAs, particularly trisomy 12, rather than gene mutations. Shared clonotypes were found both within and across groups, which appeared to be CLL-biased based on extensive comparisons against TR databases from various entities. Moreover,

Conclusions

Distinct TR repertoire profiles were identified in groups of patients with CLL bearing different genomic aberrations, alluding to distinct selection processes. Abnormal protein expression and gene dosage effects associated with recurrent genomic aberrations likely represent a relevant source of CLL-specific selecting antigens.

Informations de copyright

Copyright © 2023 Vlachonikola, Pechlivanis, Karakatsoulis, Sofou, Gkoliou, Jeromin, Stavroyianni, Ranghetti, Scarfo, Österholm, Mansouri, Notopoulou, Siorenta, Anagnostopoulos, Ghia, Haferlach, Rosenquist, Psomopoulos, Kouvatsi, Baliakas, Stamatopoulos and Chatzidimitriou.

Déclaration de conflit d'intérêts

CH declares part ownership of Munich Leukemia Laboratory MLL. SJ is employed by the MLL. RR received honoraria and is a member on the advisory board of Abbvie, AstraZeneca, Janssen, Illumina and Roche. PG received honoraria and is a member on the advisory board of AbbVie, Acerta/AstraZeneca, Adaptive, ArQule/MSD, BeiGene, CelGene/Juno, Gilead, Janssen, Loxo/Lilly, Sunesis; and also receives research funding from AbbVie, Gilead, Janssen, Novartis, Sunesis. LS received honoraria and is a member on the advisory board of AbbVie, AstraZeneca, BeiGene, Janssen; and also received travel grants from BeiGene, Janssen; Speaker bureau: Octapharma. KS received research funding from Abbvie, AstraZeneca and Abbvie and is a member on the advisory board of AbbVie, AstraZeneca, Gilead, Janssen, and Bristol Myers Squibb. AC received research funding from Abbvie, Novartis and Janssen. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.