A89
Is there are a role for immunotherapy in platinum sensitive and resistant ovarian cancer patients?
Mohamed Shehata, Abhik Mukherjee, Suha Deen, Claire Paish, Ian Spendlove, Karin Williamson, Robert Hammond, Lindy Durrant, Stephen Chan
Nottingham University Hospitals, Nottingham, UK
Background
Loss of HLA class I antigen expression has been shown to be an independent prognostic marker in ovarian cancer patients (heterogeneous for chemotherapy regimen). The current study aimed to examine the prognostic significance of HLA antigen expression in a cohort treated with platinum chemotherapy.
Method
A tissue micro-array (TMA) was constructed from 157 patients’ tumour blocks and immunohistochemistry undertaken for the HLA class 1 antigens, the heavy chain component (using HC10 antibody) and the beta-2-microglobulin (β2m) component. TMAs were scored by a semi-quantitative H-Score technique (positive if score >10). The HC10+/b2m+ phenotype was defined as HLA1 positive.
Results
106 patients (67.5%) were sensitive to platinum; 49 (31.2%) were resistant and 2 (1.3%) lost to follow up. At analysis, 75 patients (47.8%) were progression free and 103 patients (65.6%) alive. 53% were HLA class I + (HC10+ β2m+). Of the platinum sensitive patients, 60 (56.6%) were HLA1 positive. Of the 48 resistant cases evaluable, 22 (45.83%) were positive. However, HLA1 phenotype expression did not correlate significantly with platinum sensitivity. The positive phenotype correlated with better overall survival both on univariate (p=0.032) and multivariate analysis (median survival 57 months versus 34 months respectively; p=0.024). This survival difference is marked in the platinum resistant (p=0.06) compared with the sensitive group (p=0.2). Immune biomarkers (INFγ receptors and downstream signalling molecules) are being analysed.
Conclusion
Loss of HLA1 expression is a bad prognostic factor in ovarian cancer. Investigations are commencing whether immune-modulators such as INFγor NK cells may provide additional help to chemotherapy.
