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HLA Class I Antigen Processing Machinery Component Expression and Intratumoral T-Cell Infiltrate as Independent Prognostic Markers in Ovarian Carcinoma

Authors' Affiliations: Departments of ¹ Gynecologic Oncology, ² Biostatistics and Applied Mathematics, ³ Pathology, and ⁴ Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; ⁵ Department of Pathology, University of Nebraska, Omaha, Nebraska; Departments of ⁶ Obstetrics and Gynecology and ⁷ Psychology, The University of Iowa, Iowa City, Iowa; and ⁸ Department of Immunology, State University of New York-Roswell Park Cancer Center, Buffalo, New York

Requests for reprints: Anil K. Sood, Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, 1155 Herman Pressler, CPB6.3244, Unit 1362, Houston, TX 77030. Phone: 713-745-5266; Fax: 713-792-7586; E-mail: asood{at}mdanderson.org.

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), β₂ 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 β₂ 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 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.