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


METHODS
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.


CONCLUSIONS
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.
Han
Liz Y
LY
Department of Gynecologic Oncology, The University of Texas M D Anderson Cancer Center, 1155 Herman Pressler, CPB6.3244, Unit 1362, Houston, TX 77030, USA.
Fletcher
Mavis S
MS
Urbauer
Diana L
DL
Mueller
Peter
P
Landen
Charles N
CN
Kamat
Aparna A
AA
Lin
Yvonne G
YG
Merritt
William M
WM
Spannuth
Whitney A
WA
Deavers
Michael T
MT
De Geest
Koen
K
Gershenson
David M
DM
Lutgendorf
Susan K
SK
Ferrone
Soldano
S
Sood
Anil K
AK
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017951:Antigen Presentation / Q000502:physiology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D026901:Membrane Transport Proteins / Q000378:metabolism; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D011379:Prognosis; D013601:T-Lymphocytes / Q000276:immunology*; D019139:Tumor Escape / Q000276:immunology; D001613:beta 2-Microglobulin / Q000378:metabolism
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; D026901:Membrane Transport Proteins; C073119:TAP1 protein, human; D001613:beta 2-Microglobulin; C107762:tapasin; C071692:TAP2 protein, human