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

Overview

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.

publication date

  • June 1, 2008

Research

keywords

  • Antigen Presentation
  • Histocompatibility Antigens Class I
  • Lymphocytes, Tumor-Infiltrating
  • Ovarian Neoplasms
  • T-Lymphocytes

Identity

PubMed Central ID

  • PMC3426216

Scopus Document Identifier

  • 50349084447

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-07-4433

PubMed ID

  • 18519766

Additional Document Info

volume

  • 14

issue

  • 11