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EP912 Characterization of the tumour microenvironment in high-grade serous ovarian cancer (HGSOC): prognostic value of the lymphocytic infiltration patterns and immune-related genes
  1. J Marí-Alexandre1,
  2. F Herrera-Cañizares2,3,
  3. A Chipirliu4,
  4. C Caballero5,
  5. C Agababyan4,
  6. L Valdivieso6,
  7. N Santonja6,
  8. A Llueca7,8,9,
  9. S Calabuig10,11,
  10. E Jantus-Lewintre10,12,
  11. C Camps10,13,14 and
  12. J Gilabert-Estellés15,16,17
  1. 1Laboratorio Investigación Biomarcadores en Reproducción, Ginecología y Obstetricia, Fundación para la Investigación Hospital General Universitario
  2. 2Laboratorio de Oncología Molecular, Fundación de Investigación Hospital General Universitario de Valencia
  3. 3Fundación Carolina-BBVA
  4. 4Servicio de Obstetricia y Ginecología
  5. 5Servicio de Oncología Médica
  6. 6Servicio de Anatomía Patológica, Hospital General Universitario Valencia, Valencia
  7. 7Servicio de Obstetricia y Ginecología, Hospital General Universitario de Castellón, Castellón
  8. 8Unidad Multdisciplinar de Cirguía Abdominopélvica, Hospital General Universitario de Castellón, Valencia
  9. 9Departamento de Medicina, Universidad Jaume I, Castellón
  10. 10Laboratorio de Oncología Molecular, Fundación de Investigación Hospital General Universitario de Valencia-CIBERONC
  11. 11Departamento de Patología, Universitat de Valencia
  12. 12Departamento de Biotecnología, Universidad Politécnica de Valencia
  13. 13Servicio de Oncología Molecular, Hospital General Universitario de Valencia
  14. 14Departamento de Medicina, Universidad de Valencia
  15. 15Laboratorio Investigación Biomarcadores en Reproducción, Ginecología y Obstetricia, Fundación de Investigación Hospital General Universitario de Valencia
  16. 16Servicio de Obstetricia y Ginecología, Hospital General Universitario de Valencia
  17. 17Departamento de Pediatría, Obstetricia y Ginecología, Universidad de Valencia, Valencia, Spain

Abstract

Introduction/Background Lymphocytic infiltration areas (immunoreactive), frequently found in high-grade serous ovarian cancer (HGSOC), are associated with a better prognosis and increased survival. The cross-talk between tumour cells and lymphocytes conditions the capacity of the immune system (IS) to cope with the tumour in the so-called immune-checkpoints. Therefore, assessing IS-related genes and infiltration patters might provide valuable prognostic biomarkers.

Methodology This retrospective study includes 57 samples from patients with HGSOC who underwent cytoreductive surgery at Hospital General (Valencia). Clinical variables, the features of the lymphocytic infiltration (pattern, localization and degree) and the expression of immune-related genes (CD4, CD8, FOXP3, ICOSL, ICOS, PD-L2, TGFβ1, CD25, IDO1, IL7R, PD-L1, CTL4, CXCR4, PD1, OX40, LGAL and CD137) were evaluated to assess prognosis.

Results The median age was 61.5 years, being the majority of patients in advanced FIGO stages (76.3% III–IV vs. 23.7%, I–II stages). Patients with ≥65 years and III–IV stages showed a shorter overall survival (OS, 30.17 vs. 99.90 months, p=0.009; 38.73 months vs. NR, p=0.005, respectively). Regarding immunoreactive areas, patients with an intratumoural pattern of lymphocyte infiltration had better prognosis compared to those that only had a peritumoural pattern (OS: 44.57 months vs. NR, p=0.041). In addition, those with a diffuse infiltration pattern presented a better prognosis compared to those with a focal pattern (OS, 20.20 months vs. NR p=0.003). Regarding gene expression, 11 genes (CTLA4, FOXP3, CD25, CSCR4, IDO1, PD-1, PD-L1, PD-L2, OX40L, ICOS, ICOSL, LGAL9 and CD137 were found over-expressed, but only CD137 displayed a significant prognostic value (OS: 50 months vs NR, p=0.020)

Conclusion HGSOC represents a group of highly immunoreactive tumours. Best prognosis is represented by patients with an intratumoural and diffuse pattern of lymphocytic infiltration and lower CD137 expression, which may be considered as valuable prognostic markers. These interesting findings could open a new window for immunotherapeutic approaches in HGSOC.

Disclosure All authors have declared no conflicts of interest. This work has been supported by grants from ISCIII (PI17/01945 and CB16/12/00350). J.M-A. is supported by APOSTD/2019/087 post-doctoral grant.

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