Circulating T-cell receptor diversity as predictive biomarker for PARP inhibitors maintenance therapy in high grade serous ovarian cancer

Gynecol Oncol. 2023 Jan;168:135-143. doi: 10.1016/j.ygyno.2022.11.013. Epub 2022 Nov 25.

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: Maintenance therapy; Ovarian cancer; PARP inhibitor; Predictive biomarker; TCR diversity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / therapeutic use
  • Biomarkers
  • Female
  • Humans
  • Ovarian Neoplasms* / drug therapy
  • Poly(ADP-ribose) Polymerase Inhibitors / pharmacology
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
  • Receptors, Antigen, T-Cell

Substances

  • Poly(ADP-ribose) Polymerase Inhibitors
  • Antineoplastic Agents
  • Biomarkers
  • Receptors, Antigen, T-Cell