Highlights
- •The TCR repertoire was more stable in patients with high grade serous ovarian cancer following PARPi maintenance therapy.
- •An increase in TCR diversity after three months of PARPi maintenance may predict a better response to PARPi treatment.
- •Patients who responded better to PARPi treatment showed a decrease of high-frequency TCR clones.
Abstract
Objective
T-cell receptor (TCR) repertoire diversity is getting increasing attention as a predictive
biomarker in cancer patients. However, the characteristics of the TCR together with
its predictive significance for high grade serous ovarian cancer (HGSOC) patients
receiving poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy remain
unknown.
Methods
Twenty-seven patients with HGSOC were analyzed including 22 patients receiving PARPi
maintenance therapy and 5 untreated patients as control. Peripheral blood samples
were collected for TCR sequencing at baseline as well as one month and three months
after the exposure to PARPi. To determine whether TCR diversity was related to PARPi
efficacy, we compared the TCR repertoire between patients who had received PARPi and
those who had not.
Results
For patients receiving PARPi treatment or not, we evaluated changes in clone abundance
during PARPi maintenance and the similarity of the TCR repertoire before and after
the treatment. The results revealed that patients receiving PARPi had TCR repertoires
that were more stable than those of untreated cases. We next correlated TCR diversity
with the efficacy of PARPi in the treatment group. The rising trend of TCR diversity
after three months with PARPi treatment was associated with a longer PFS (21.7 vs
7.4 months, hazard ratio = 0.19, p < 0.001) and a better response to PARPi (91.7% vs 25.0%, p = 0.004). Furthermore, we discovered that the primary characteristic with predictive
value for the effectiveness of PARPi is the considerable reduction of the high-frequency
T cell clones.
Conclusion
We suggested that the circulating TCR diversity could be a potential predictive biomarker
for PARPi maintenance therapy in HGSOC.
Keywords
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Article info
Publication history
Published online: November 25, 2022
Accepted:
November 13,
2022
Received in revised form:
October 17,
2022
Received:
June 17,
2022
Identification
Copyright
© 2022 Published by Elsevier Inc.
