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 (TCRgamma) 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 TCRgamma 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).


CONCLUSIONS
Improved survival of ovarian cancer patients is related to the infiltration, clonal selection and intraepithelial persistence of T lymphocytes.
Department of Obstetrics and Gynecology, Albert-Ludwigs-University, Freiburg 79106, Germany.
M
M
Stumpf
A
A
Hasenburg
M-O
MO
Riener
U
U
Jütting
C
C
Wang
Y
Y
Shen
M
M
Orlowska-Volk
P
P
Fisch
Z
Z
Wang
G
G
Gitsch
M
M
Werner
S
S
Lassmann
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000401:mortality* / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis
D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human