Tissue-based immune monitoring II: multiple tumor sites reveal immunologic homogeneity in serous ovarian carcinoma.

Details

Serval ID
serval:BIB_9322C0130E4C
Type
Article: article from journal or magazin.
Collection
Publications
Title
Tissue-based immune monitoring II: multiple tumor sites reveal immunologic homogeneity in serous ovarian carcinoma.
Journal
Cancer Biology and Therapy
Author(s)
Hagemann A.R., Hagemann I.S., Cadungog M., Hwang W.T., Patel P., Lal P., Hammond R., Gimotty P.A., Chu C.S., Rubin S.C., Birrer M.J., Powell D.J., Feldman M.D., Coukos G.
ISSN
1555-8576 (Electronic)
ISSN-L
1538-4047
Publication state
Published
Issued date
2011
Volume
12
Number
4
Pages
367-377
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
The presence of tumor-infiltrating lymphocytes (TILs) in epithelial ovarian cancer indicates a host antitumor response and is associated with improved survival. We wished to determine the extent to which TIL density differs from site to site within a given patient. We initially studied multiple paired metastases from serous ovarian carcinoma obtained at the time of primary debulking. The expression of genes in specific immune-related pathways was profiled on a pilot set of five patients. We then used immunohistochemistry and quantitative PCR to estimate the density of CD3+, CD8+, and FoxP3+ TILs in these same tumors. To extend the findings to a larger cohort, we semiquantitatively measured intraepithelial and stromal TILs in a tissue microarray (TMA) containing both primary tumors and metastases from 50 patients. In the pilot group, genes related to antimicrobial signaling and TGF-beta signaling showed between-site heterogeneity, whereas cytokines and antigen presentation transcripts were more homogeneous in any given patient. IHC and qPCR for T cell markers were concordant. In the TMA cohort, 2-way ANOVA showed that TIL heterogeneity between sites was present in some but not all patients. The stroma of extra-ovarian metastases showed significantly greater TIL infiltration than ovarian sites. A simulation showed that at clinically meaningful levels of precision, up to 3% of patients will be misclassified for intraepithelial TILs by a single biopsy. In conclusion, between-site heterogeneity exists in some patients with metastatic serous ovarian cancer. The predictive value of biopsies should be considered in clinical trial design.
Keywords
Aged, Antigens, CD3/genetics, Antigens, CD3/immunology, Antigens, CD4/genetics, Antigens, CD4/immunology, Antigens, CD8/genetics, Antigens, CD8/immunology, Cluster Analysis, Cohort Studies, Cystadenocarcinoma, Serous/genetics, Cystadenocarcinoma, Serous/immunology, Epithelial Cells/immunology, Epithelial Cells/metabolism, Female, Forkhead Transcription Factors/genetics, Forkhead Transcription Factors/immunology, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Immunohistochemistry, Kaplan-Meier Estimate, Lymphocytes, Tumor-Infiltrating/immunology, Lymphocytes, Tumor-Infiltrating/metabolism, Middle Aged, Monitoring, Immunologic/methods, Oligonucleotide Array Sequence Analysis, Ovarian Neoplasms/genetics, Ovarian Neoplasms/immunology, Reverse Transcriptase Polymerase Chain Reaction, Stromal Cells/immunology, Stromal Cells/metabolism, Tissue Array Analysis/methods
Pubmed
Web of science
Create date
14/10/2014 11:43
Last modification date
20/08/2019 14:56
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