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780 Treatment of ovarian cancer cells with olaparib and trabectedin modulates the expression of immune-related molecules and the killing ability of TCR-edited T cells
  1. Alice Bergamini1,
  2. Elena Tassi2,
  3. Federica Trippitelli2,
  4. Maria Chiara Maffia2,
  5. Massimo Candiani1,
  6. Luca Bocciolone1,
  7. Giorgio Candotti1,
  8. Giacomo Pavone1,
  9. Mariangela Parretta1,
  10. Emanuela Rabaiotti1,
  11. Raffaella Cioffi1,
  12. Francesca Pella1,
  13. Federica Galli1,
  14. Alessia Potenza2,
  15. Beatrice Cianciotti2,
  16. Zulma Magnani2,
  17. Eliana Ruggiero2,
  18. Giorgia Mangili1 and
  19. Chiara Bonini2
  1. 1Department of Obstetrics and Gynecology, IRCCS San Raffaele Hospital, Milan, Italy
  2. 2Experimental Hematology Unit, Department of Immunology, IRCCS San Raffaele Hospital, Milan, Italy


Introduction/Background The presence of an immune-reactive tumor microenvironment in epithelial ovarian cancer (EOC) has boosted the development of immunotherapeutic strategy, that unfortunately have shown limited clinical efficacy. Our aim is to investigate the possible immunomodulatory effect of Olaparib and Trabectedin and whether such treatments might impact on the activity of tumor-specific T cells.

Methodology In vitro dose finding assays for Olaparib and Trabectedin were conducted on 2 EOC cell lines and 3 patient-derived primary cultures by Incucyte® live cell imaging and flow cytometry (FC). The expression of inhibitory receptor (IR) ligands, activation molecules and tumor associated antigens (TAAs) was evaluated by FC after treatments with sub-optimal doses of each drug. The combined effect of drug treatment and T cells harbouring engineered tumor-specific T-cell receptors (TCRs) was also assessed in co-culture assays on both EOC cell lines and EOC primary cultures.

Results After 24-hours treatment of EOC cells with Olaparib and Trabectedin, we found a significant modulation of some IR ligands such as PD-L1, PD-L2 and CD48 and of MHC class-I molecules. Drug treatments significantly modulated the expression of NY-ESO-1, MUC-1 and WT-1 TAAs. Furthermore, 24-hours pre-treatment with each drug before co-culture with tumor-specific TCR-edited T lymphocytes increased tumor cell death on both EOC cells and primary cultures.

Conclusion Our data show that Olaparib and Trabectedin modulate the expression of immune-related molecules on EOC cells, and this effect is associated with an increased killing by tumor-specific TCR-edited T cells. Biological mechanisms at the basis of these findings deserve further investigation.

Disclosures None

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