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

Lizy Han, Mavis S. Fletcher, Diana L. Urbauer, Peter Mueller, Charles N. Landen, Aparna A. Kamat, Yvonne G. Lin, William M. Merritt, Whitney A. Spannuth, Michael T. Deavers, Koen De Geest, David M. Gershenson, Susan K. Lutgendorf, Soldano Ferrone, Anil K. Sood

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

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-inf irtratingTcells 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.

Original languageEnglish (US)
Pages (from-to)3372-3379
Number of pages8
JournalClinical Cancer Research
Volume14
Issue number11
DOIs
StatePublished - Jun 1 2008
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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