The importance of the level of T-cell receptor excision circles and κ-deletion B-cell receptor excision circles in the effectiveness of therapy for metastatic ovarian cancer

Background. Antigen load, expression of programmed cell death ligand 1 and T-cell receptors play a key role in the formation of specific antitumor immunity. The marker of the diversity of the repertoire of receptors of immunocompetent cells to various antigens are T-cell receptor excision circles (TREC) and the κ-deletion B-cell receptor excision circles (KREC), which are extrachromosomal DNA structures. Aim. To evaluate the effect of the diversity of TREC and KREC on the effectiveness of olaparib therapy for generalized ovarian cancer. Materials and methods. The study included 40 patients undergoing treatment at the Republican Clinical Oncological Dispensary (RCOD) of the Ministry of Health of the Republic of Bashkortostan for ovarian cancer. The local ethics committee of RCOD approved on July 21, 2022 the protocol “IO-001” of a single-center non-randomized open clinical trial entitled “Determination of TREC and KREC in patients with malignant neoplasms of various localizations”. All patients were prescribed olaparib therapy (international non-proprietary name). To identify mutations in genes associated with HRD (homologous recombination deficiency), next-generation sequencing by allele-specific polymerase chain reaction was used. Before the start of therapy, the level of TREC and KREC was assessed. Results. Before the start of therapy in the general population, the median TREC was 9.6 copies/105 cells, the median KREC was 183.8 copies/105 cells. The minimum and maximum TREC levels were 0.07 copies/105 cells and 215 copies/105 cells, respectively. The minimum and maximum KREC levels were 2.8 copies/105 cells and 1559.42 copies/105 cells, respectively. In the group of patients with disease progression, the level of TREC was low. According to the results of the study, disease progression was predicted at a TREC value 13.23 copies/105 cells. The obtained results indicate a significantly low level of KREC before the start of therapy in patients who progressed during therapy. Conclusion. The prognostic role of TREC and KREC has been determined. Further research will allow us to take into account changes in TREC and KREC indicators in dynamics and use the prognostic value of these changes in the treatment of ovarian cancer. Threshold levels of TREC (13.23 copies/105 cells) and KREC (251.04 copies/105 cells) were detected, below which disease progression was observed.