T cell infiltration and MHC I and II expression in the presence of tumor antigens: An immunohistochemical study in patients with serous epithelial ovarian cancer.
OBJECTIVE
Ovarian cancer is a frequent cause of death among women with gynaecologic malignancies despite the introduction of combination chemotherapy. There is therefore a need for new therapeutic strategies for patients with ovarian cancer, such as cellular immunotherapy. In this immunohistochemical study we analysed the expression of three tumor antigens, p53, HER-2/neu and MUC-1 in relation to the expression of major histocompatibility complex (MHC) class I and II on tumor cells, and we searched for the presence of (activated) immune effector cells at the tumor site.


METHODS
The study was carried out retrospectively in tumor tissue from 29 patients with serous ovarian cancer. Material used had been formalin fixed and paraffin embedded. Material had been obtained from 15 patients at staging laparotomy and from 14 patients during second look or intervention laparotomy.


RESULTS
A positive staining for p53 was found in 19/29 (66%) of the tumors, with a high positivity in 13/29 (45%). HER-2/neu and MUC-1 staining was positive in 8/29 (28%) and 21/28 (75%), respectively. Downregulation of MHC class I on tumor cells was found in a minority of the patients, beta-2-microglobin (beta2m) was expressed on tumor cells in all patients. High staining for CD45RO correlated with a high positive staining for granzyme-B (R=0.40, P=0.04) and TIA-1 (R=0.39, P=0.04). A statistically significant better survival in the group with lower stage of disease was found.


CONCLUSIONS
As only three out of 29 patients were negative for the tumor antigens p53, HER-2/neu and MUC-1, immunotherapy aiming at all three could serve almost all patients with ovarian cancer. We found that granzyme-B, TIA-1 and CD45RO+ T cells are present in the tumor biopsies, increasing this number by immunotherapy may be beneficial. The immune escape mechanism by MHC class I and beta2m downregulation seems to be of minor importance. Our data support the view that immunotherapy may offer new possibilities with high specificity in ovarian cancer.
Nijman
H W
HW
Department of Obstetrics and Gynaecology, University Hospital Vrije Universteit, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands.
van Diest
P J
PJ
Poort-Keesom
R J
RJ
von Mensdorff-Pouilly
S
S
Verstraeten
R A
RA
Kummer
A
A
Meijer
C J
CJ
Melief
C J
CJ
Hilgers
J
J
Kenemans
P
P
D000328:Adult; D000951:Antigens, Neoplasm / Q000032:analysis*; D018284:Cystadenocarcinoma, Serous / Q000276:immunology* / Q000473:pathology; D005260:Female; D053804:Granzymes; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis; D008875:Middle Aged; D018396:Mucin-1 / Q000032:analysis; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology; D039102:Poly(A)-Binding Proteins; D011506:Proteins; D016601:RNA-Binding Proteins / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D012189:Retrospective Studies; D012697:Serine Endopeptidases / Q000032:analysis; D000074019:T-Cell Intracellular Antigen-1; D013601:T-Lymphocytes / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D000951:Antigens, Neoplasm; D053804:Granzymes; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D017493:Leukocyte Common Antigens; D008565:Membrane Proteins; D018396:Mucin-1; D039102:Poly(A)-Binding Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D012697:Serine Endopeptidases; D000074019:T-Cell Intracellular Antigen-1; D016159:Tumor Suppressor Protein p53; C071558:TIA1 protein, human; C509213:GZMB protein, human