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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