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

Abstract

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 ¼ 100), and for Her2/neu-positive tumour cells (n ¼ 55/100) by immunohistochemistry. Clonality analysis was carried out by T-cell receptor g (TCRg) gene rearrangements (n ¼ 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 ¼ 0.0402). Intraepithelial CD8-positive T lymphocytes were correlated with improved OS in all optimally debulked patients (P ¼ 0.0201) and in those undergoing paclitaxel/carboplatin therapy (P ¼ 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 ¼ 0.0873). Despite a significant correlation of HER2/neu status and intraepithelial CD8-positive lymphocytes (P ¼ 0.0264), this was non-directional (R ¼ À0.257; P ¼ 0.0626). CONCLUSION: Improved survival of ovarian cancer patients is related to the infiltration, clonal selection and intraepithelial persistence of T lymphocytes.

A Comprehensive Analysis of Human Gene Expression Profiles Identifies Stromal Immunoglobulin κ C as a Compatible Prognostic Marker in Human Solid Tumors

“…However, most often the clinical relevance was ascribed to the T-cell lineage, with predominance of CD8 þ , and CD45RO þ T lymphocytes in colorectal, lung, and ovarian cancer (22)(23)(24)(25). The immune infiltrates in breast cancer have been characterized recently.…”

Tumor infiltrating lymphocytes in ovarian cancer

“…17 Similar results have been reported extensively elsewhere. [18][19][20][21][22][23][24][25][26][27][28][29][30][31] Three other studies indicate that both CD3 and CD8C TILs are of good prognosis in ovarian cancer. [32][33][34] While CD8C TILs appear to be best associated with improved survival, still other reports indicate that CD4C TILs are the subset of value in prognosticating ovarian cancer.…”

Evaluation of Inflammatory Cells (Tumor Infiltrating Lymphocytes) in Solid Tumors

“…Co se týká metodiky hodnocení TIL, u ovariálních karcinomů byly hodnoceny pouze intratumorózní lymfocytyvětšina studií zdůrazňuje pozitivní prognostický význam intraepiteliálně lokalizovaných lymfocytů [77,78] a pouze ve dvou studiích byl oproti tomu proká-zán pozitivní prognostický význam stromálních lymfocytů [79,80]. Metodika prací byla značně nejednotná, lymfocyty byly počítány jak manuálně, tak metodami digitální analýzy, byly užity různé hranice pozitivity, lišil se i počet zorných polí a velikost zvětšení [78].…”