Intraepithelial CD8-positive T lymphocytes predict survival for patients with serous stage III ovarian carcinomas: Relevance of clonal selection of T lymphocytes

Background: The aim of this study was to investigate the prognostic effect of tumour-infiltrating lymphocytes (TILs) in serous stage III ovarian carcinoma to determine TIL clonality and to correlate this to Her2/neu expression.Methods:Formalin-fixed and paraffin-embedded ovarian carcinomas were examined for CD20-, CD3-, CD4-and CD8-positive lymphocytes (n100), and for Her2/neu-positive tumour cells (n55/100) by immunohistochemistry. Clonality analysis was carried out by T-cell receptor γ (TCRγ) gene rearrangements (n93/100). Statistical analyses included experimental and clinico-pathological variables, as well as disease-free (DFS) and overall (OS) survival.Results:CD20-positive B lymphocytes were present in 57.7% (stromal)/33.0% (intraepithelial) and CD3-positive T lymphocytes in 99.0% (stromal)/90.2% (intraepithelial) of ovarian carcinomas. Intraepithelial CD3-positive T lymphocytes were correlated with improved DFS in optimally debulked patients (P0.0402). Intraepithelial CD8-positive T lymphocytes were correlated with improved OS in all optimally debulked patients (P0.0201) and in those undergoing paclitaxel/carboplatin therapy (P0.0092). Finally, rarified and clonal TCRγ gene rearrangements were detected in 37 out of 93 (39.8%) and 15 out of 93 (16.1%) cases, respectively. This was marginally associated with improved DFS (P0.0873). Despite a significant correlation of HER2/neu status and intraepithelial CD8-positive lymphocytes (P0.0264), this was non-directional (R0.257; P0.0626).Conclusion:Improved survival of ovarian cancer patients is related to the infiltration, clonal selection and intraepithelial persistence of T lymphocytes.