Systematic analysis of immune infiltrates in high-grade serous ovarian cancer reveals CD20, FoxP3 and TIA-1 as positive prognostic factors.
BACKGROUND
Tumor-infiltrating T cells are associated with survival in epithelial ovarian cancer (EOC), but their functional status is poorly understood, especially relative to the different risk categories and histological subtypes of EOC.


RESULTS
Tissue microarrays containing high-grade serous, endometrioid, mucinous and clear cell tumors were analyzed immunohistochemically for the presence of lymphocytes, dendritic cells, neutrophils, macrophages, MHC class I and II, and various markers of activation and inflammation. In high-grade serous tumors from optimally debulked patients, positive associations were seen between intraepithelial cells expressing CD3, CD4, CD8, CD45RO, CD25, TIA-1, Granzyme B, FoxP3, CD20, and CD68, as well as expression of MHC class I and II by tumor cells. Disease-specific survival was positively associated with the markers CD8, CD3, FoxP3, TIA-1, CD20, MHC class I and class II. In other histological subtypes, immune infiltrates were less prevalent, and the only markers associated with survival were MHC class II (positive association in endometrioid cases) and myeloperoxidase (negative association in clear cell cases).


CONCLUSIONS
Host immune responses to EOC vary widely according to histological subtype and the extent of residual disease. TIA-1, FoxP3 and CD20 emerge as new positive prognostic factors in high-grade serous EOC from optimally debulked patients.
Milne
Katy
K
Trev and Joyce Deeley Research Centre, BC Cancer Agency, Victoria, British Columbia, Canada.
Köbel
Martin
M
Kalloger
Steven E
SE
Barnes
Rebecca O
RO
Gao
Dongxia
D
Gilks
C Blake
CB
Watson
Peter H
PH
Nelson
Brad H
BH
D018951:Antigens, CD20 / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D014408:Biomarkers, Tumor / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology; D039102:Poly(A)-Binding Proteins / Q000276:immunology*; D011379:Prognosis; D016019:Survival Analysis; D000074019:T-Cell Intracellular Antigen-1; D046888:Tissue Array Analysis
D018951:Antigens, CD20; D014408:Biomarkers, Tumor; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D039102:Poly(A)-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human