Endogenous immune responses in breast and ovarian cancers

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Initially pathologists were the first to suggest that intrinsic antitumor immune response could be generated in vivo in breast cancer. Black described lymphoid infiltration of primary breast tumors and sinus histiocytosis of regional lymph nodes (2). Tumor-infiltrating lymphocytes (TILs) have been identified in ovarian adenocarcinoma tissue as well as peritoneal malignant ascites (3-5). The isolation of TILs with activity against specific TAAs has allowed characterization of specific antigens.

For example, MUC-1 is a transmembrane glycoprotein expressed on the apical surface of normal glandular epithelial cells. It has multiple tandem peptide repeats that offer potential antigen sources for dendritic cell (DC) presentation. MUC-1 is overexpressed in adenocarcinomas including breast, pancreatic, and ovarian. When expressed on cancers, MUC-1 tends to be aberrantly glycosylated and expressed on the entire cell surface, rather than luminally as on normal cells (6,7). MUC-1 overexpression is also correlated with progression of ovarian cancer (8). MUC-1-specific cytotoxic T lymphocytes (CTLs) have been isolated from involved lymph nodes (9), ascites (10-12), and tumor tissue (13) in ovarian malignancies, as well as in draining lymph nodes in pancreatic and breast cancer patients (3,14). Because of its high surface-expression levels, aberrant tumor-associated glycosylation resulting in exposure of normally masked peptide epitopes, and broad expression across several tumor types, MUC-1 is a favored target in cancer vaccine trials.

Though most clinical trials attempt to generate cellular immunity, there is perhaps stronger evidence of endogenous humoral antitumor immune responses. Circulating levels of immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies complexed to MUC-1 have been demonstrated in the sera of breast and ovarian cancer patients (15,16). Although MUC-1 antibodies can also be demonstrated in pregnant women (17), over 50% of ovarian cancer patients have measurable levels of circulating MUC-1 antibodies that are typically at higher levels than those observed in control and pregnant subjects (18).

In breast cancer, immune activity has correlated with clinical outcomes in several studies. Histologic lymphoid infiltrates in primary breast tumors have been associated with improved survival (19). Elevated anti-MUC-1 IgG and IgM levels in stage I and II breast cancer patients have also predicted improved disease specific outcomes (20). Antitumor antibodies detected pretreament in early-stage breast cancer patients have also

Table 1

Nonspecific Immune Modulators

Table 1

Nonspecific Immune Modulators

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