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 (n = 100), and for Her2/neu-positive tumour cells (n = 55/100) by immunohistochemistry. Clonality analysis was carried out by T-cell receptor gamma (TCR gamma) gene rearrangements (n = 93/100). 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 (P = 0.0402). Intraepithelial CD8- positive T lymphocytes were correlated with improved OS in all optimally debulked patients (P = 0.0201) and in those undergoing paclitaxel/carboplatin therapy (P = 0.0092). Finally, rarified and clonal TCRg 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 (P = 0.0873). Despite a significant correlation of HER2/neu status and intraepithelial CD8- positive lymphocytes (P = 0.0264), this was non-directional (R = -0.257; P = 0.0626). CONCLUSION: Improved survival of ovarian cancer patients is related to the infiltration, clonal selection and intraepithelial persistence of T lymphocytes. British Journal of Cancer ( 2009) 101, 1513-1521. doi: 10.1038/sj.bjc.6605274 www.bjcancer.com Published online 29 September 2009 (C) 2009 Cancer Research UK