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Clin Cancer Res. 2008 Jun 1;14(11):3372-9. doi: 10.1158/1078-0432.CCR-07-4433.

HLA class I antigen processing machinery component expression and intratumoral T-Cell infiltrate as independent prognostic markers in ovarian carcinoma.

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1
Department of Gynecologic Oncology, The University of Texas M D Anderson Cancer Center, 1155 Herman Pressler, CPB6.3244, Unit 1362, Houston, TX 77030, USA.

Abstract

PURPOSE:

Defects in the antigen processing machinery (APM) may provide tumor cells with a mechanism to escape immune recognition. The purpose of this study is to determine the clinical significance of APM component down-regulation and tumor-infiltrating T cells in ovarian carcinoma.

EXPERIMENTAL DESIGN:

After institutional review board approval, tumor samples from 150 patients with invasive epithelial ovarian cancers were examined for TAP1, TAP2, tapasin, HLA class I heavy chain (HLA-HC), beta 2 microglobulin, and T-cell (CD3+ and CD8+) tumor infiltration using immunohistochemistry.

RESULTS:

The majority of tumors had either heterogeneous or positive expression of TAP1, TAP2, HLA-HC, and beta 2 microglobulin (66.7%, 73.3%, 70.7%, and 63.3%, respectively), except tapasin for which 58% of the tumors lacked expression. Furthermore, 67% and 88% of the lesions possessed intratumoral and peritumoral CD3+ or CD8+ cells, respectively. The majority of APM component expression examined was significantly associated with both intratumoral and peritumoral T-cell infiltration (P < 0.05). The expression of APM components and the presence of intratumoral T-cell infiltrates were significantly associated with improved survival (all P < or = 0.01); however, peritumoral T-cell infiltrates did not significantly affect survival (P = 0.33). APM component down-regulation (P < 0.001), lack of intratumoral T-cell infiltrates (P = 0.03), and suboptimal cytoreduction (P < 0.001) were independent prognostic markers for death from ovarian carcinoma.

CONCLUSION:

The negative effect of APM component down-regulation by itself and in combination with absent intratumoral T-cell infiltration on the survival of patients with ovarian carcinoma implies a role for immune escape in addition to immunosurveillance in the clinical course of disease.

PMID:
18519766
PMCID:
PMC3426216
DOI:
10.1158/1078-0432.CCR-07-4433
[Indexed for MEDLINE]
Free PMC Article
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