Tumor-infiltrating T cells correlate with NY-ESO-1-specific autoantibodies in ovarian cancer

• Published in: PloS one Vol. 3; no. 10; p. e3409
• Main Authors: Milne, Katy, Barnes, Rebecca O, Girardin, Adam, Mawer, Melanie A, Nesslinger, Nancy J, Ng, Alvin, Nielsen, Julie S, Sahota, Robert, Tran, Eric, Webb, John R, Wong, May Q, Wick, Darin A, Wray, Andrew, McMurtrie, Elissa, Köbel, Martin, Kalloger, Steven E, Gilks, C Blake, Watson, Peter H, Nelson, Brad H
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15.10.2008; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Aged, 80 and over; Antigen (tumor-associated); Antigens; Antigens, Neoplasm - immunology; Ascites; Autoantibodies; Autoantibodies - blood; Autoantibodies - immunology; Autoimmunity; Biochemistry; Cancer; Cancer therapies; CD20 antigen; CD25 antigen; CD3 antigen; CD4 antigen; CD4-Positive T-Lymphocytes; CD8 antigen; CD8-Positive T-Lymphocytes; Cell survival; Chemotherapy; Clinical outcomes; Correlation; Cytokines; Enzyme-linked immunosorbent assay; Female; Foxp3 protein; Granzyme B; Histocompatibility antigen HLA; HLA antigens; Hospitals; Humans; Identification methods; Immunoglobulin G; Immunohistochemistry; Immunology; Immunology/Immune Response; Immunotherapy; Interferon; Lymphocyte Count; Lymphocytes; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - immunology; Major histocompatibility complex; Markers; Medical prognosis; Medical research; Membrane Proteins - immunology; Middle Aged; Oncology; Ovarian cancer; Ovarian carcinoma; Ovarian Neoplasms - immunology; Pathology; Patients; Studies; Surgery; T cell receptors; T cells; Tumor antigens; Tumor cells; Tumors; Women's Health/Gynecological Cancers; γ-Interferon; Vancouver British Columbia Canada; Canada
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0003409

Tumor-infiltrating CD8+ T cells are correlated with prolonged progression-free and overall survival in epithelial ovarian cancer (EOC). A significant fraction of EOC patients mount autoantibody responses to various tumor antigens, however the relationship between autoantibodies and tumor-infiltrating T cells has not been investigated in EOC or any other human cancer. We hypothesized that autoantibody and T cell responses may be correlated in EOC and directed toward the same antigens. We obtained matched serum and tumor tissue from 35 patients with high-grade serous ovarian cancer. Serum samples were assessed by ELISA for autoantibodies to the common tumor antigen NY-ESO-1. Tumor tissue was examined by immunohistochemistry for expression of NY-ESO-1, various T cell markers (CD3, CD4, CD8, CD25, FoxP3, TIA-1 and Granzyme B) and other immunological markers (CD20, MHC class I and MHC class II). Lymphocytic infiltrates varied widely among tumors and included cells positive for CD3, CD8, TIA-1, CD25, FoxP3 and CD4. Twenty-six percent (9/35) of patients demonstrated serum IgG autoantibodies to NY-ESO-1, which were positively correlated with expression of NY-ESO-1 antigen by tumor cells (r = 0.57, p = 0.0004). Autoantibodies to NY-ESO-1 were associated with increased tumor-infiltrating CD8+, CD4+ and FoxP3+ cells. In an individual HLA-A2+ patient with autoantibodies to NY-ESO-1, CD8+ T cells isolated from solid tumor and ascites were reactive to NY-ESO-1 by IFN-gamma ELISPOT and MHC class I pentamer staining. We demonstrate that tumor-specific autoantibodies and tumor-infiltrating T cells are correlated in human cancer and can be directed against the same target antigen. This implies that autoantibodies may collaborate with tumor-infiltrating T cells to influence clinical outcomes in EOC. Furthermore, serological screening methods may prove useful for identifying clinically relevant T cell antigens for immunotherapy.