Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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

Liz Y Han  1 , 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
Affiliations

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

Liz Y Han et al. Clin Cancer Res. .

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.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Representative staining pattern of APM components and T cells. A, staining patterns for negative versus positive (including heterogeneous) immunostaining in epithelial ovarian carcinoma. Original magnification, ×100. B, immunohistochemical staining patterns for positive CD3+ and CD8+ T cells. Solid arrow, CD3+ T cell in the peritumoral tissue; open arrow, intratumoral CD3+ T cell. Borders of tumor and stroma tissues are demarcated by white dotted lines. Original magnification, ×200. C, distribution of staining patterns for the various APM components in epithelial ovarian cancers. D, distribution of staining patterns for the CD3+/CD8+ T cells. IT, intratumoral; PT, peritumoral.
Fig. 2
Fig. 2
Kaplan Meier survival curves for ovarian carcinoma patients based on the presence (solid lines) or absence (dotted lines) of APM components or tumoral T cells. A, TAP1 (HR, 0.38; 95% CI, 0.25–0.57), median survival of 4.08 y for patients with intact expression versus 1.75 y for patients with absent expression; B, TAP2 (HR, 0.32; 95% CI, 0.21–0.49), median survival of 3.97 y versus 1.78 y. C, tapasin (HR, 0.39; 95% CI, 0.26–0.81), median survival of 5.75 y versus 1.98 y. D, HLA-HC (HR, 0.57; 95% CI, 0.38–0.85), median survival of 3.92 y versus 1.92 y. E, β2 microglobulin (β2m; HR, 0.54; 95% CI, 0.36–0.81), median survival of 3.95 y versus 1.92 y. F, response by number of APM components expressed: solid line, presence of all five APM components; dashed line, one to four components intact (HR, 1.95; 95% CI, 1.21–3.14); dotted line, complete absence of all five components (HR, 4.74; 95% CI, 2.40–9.36). Median survival of 1.44 y (none) versus 2.58 y (1–4 APM component expressed) versus 5.67 y (all five APM components expressed). G, intratumoral CD3+ or CD8+ T cells (HR, 2.04; 95% CI, 1.35–3.07), median survival 1.67 y versus 3.79 y. H, peritumoral CD3+ or CD8+ T cells (HR, 1.32; 95% CI, 0.75–2.33), median survival of 2 y versus 3.02 y.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Cancer Facts and Figures 2007. American Cancer Society; Atlanta (GA): 2007.
    1. Agarwal R, Kaye SB. Ovarian cancer: strategies for overcoming resistance to chemotherapy. Nat Rev Cancer. 2003;3:502–16. - PubMed
    1. Palena C, Abrams SI, Schlom J, Hodge JW. Cancer vaccines: preclinical studies and novel strategies. Adv Cancer Res. 2006;95:115–45. - PubMed
    1. Steinman RM, Mellman I. Immunotherapy: bewitched, bothered, and bewildered no more. Science. 2004;305:197–200. - PubMed
    1. Blattman JN, Greenberg PD. Cancer immunotherapy: a treatment for the masses. Science. 2004;305:200–5. - PubMed

Publication types

MeSH terms

Substances