Cell-surface expression of complement restriction factors and sialyl Lewisantigens in oral carcinoma: Relevance to chemo-immunotherapy

Oral squamous cell carcinomas overexpress tumor-associated antigens, yet th ese antigens do not induce an immune-mediated anti-tumor response. The abse nce of an antitumor immune response may be due to poor immunogenicity of th e tumor antigens or due to presence of factors that restrict immune functio ns. We have analyzed the expression tumor-associated sialyl Lewis(A) (sLe(A )) and sialyl Lewis(X) of the tumor-associated sialyl Lewd (sLe(A)) ann sia lyl Lewis(X) (sLeA) antigens, the complement restriction factors (CD59, CD4 6 and CD55) and the apoptosis associated factors Fas and Fas Ligand. Sialyl Lewis antigens (sLe(A) and sLe(X)), are immunogenic in that they elicit co mplement-fixing IgM antibodies. These antigens ale associated with aggressi ve invasive behavior, tumor progression and pool disease-free survival of p atients with human carcinomas. Human oral squamous carcinoma cell lints, SC C12 and SCC71, were analyzed for the density of Sialyl Lewis antigens, CD59 , CD46, CD59, Fas and Fast on the cell surface. Expression of these antigen s on the cell surface was determined employing a cell- suspension ELISA wit h monospecific monoclonal antibodies. In both oral carcinoma cell lints, th e density of expression of sLe(X) was higher than that of sLe(A) and SCC71 had a very low level of sLe(A) expression. Both cell lines expressed a high density of CD59 and slightly lower levels of CD46 and CD55 on the cell sur face suggesting that even if host antibodies are accessible to the target a ntigens such as sLe(X), they could not mediate complement-dependent cytotox icity. The SCC lines expressed very low levels of Fas and FasL indicating t hat there maybe a lack of these signaling molecules for apoptosis. Our data suggests that passive immunotherapy or tumor killing by antibody-complemen t interaction may require downregulation of complement restriction factors.