EP285/#110 Circulating T-cell receptor diversity as prognostic biomarker for PARP inhibitors maintenance therapy in high-grade serous ovarian cancer

Objectives

T-cell receptor (TCR) repertoire diversity is getting increasing attention as prognostic biomarker in cancer patients. However, the characteristics of the TCR together with its prognostic significance and impact on high grade serous ovarian cancer (HGSOC) patients receiving poly (ADP-ribose) polymerase (PARP) inhibitor maintenance therapy remain unknown.

Methods

We investigated the TCR repertoire diversity by high-throughput sequencing in peripheral blood samples from 27 patients at three timepoints of each case before, one month and three months after the exposure to PARP inhibitors respectively.

Results

Our results revealed that PARP inhibitors could maintain the stability of TCR repertoire compared to the untreated cases in the maintenance setting. And the rising trend of TCR repertoire diversity in blood after 3-month PARPi maintenance was associated with a longer PFS while low repertoire diversity change was linked with poor prognosis. Furtherly, the significant reduction of the high-frequency clone of TCR was found to be the leading characteristic and hold the potential to be a prognostic biomarker for PARP inhibitors maintenance therapy in HGSOC.

Conclusions

Interestingly, we found the dynamic monitoring of circulating TCR repertoire diversity has predictive value on the benefit of PARP inhibitor maintenance therapy in high-grade serous ovarian cancer.