Article: article from journal or magazin.
Tissue-based immune monitoring II: multiple tumor sites reveal immunologic homogeneity in serous ovarian carcinoma.
Cancer Biology and Therapy
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
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.
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
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