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

Narendranath M H Ravindranath, Kevin Nishimoto, Kyo Chu, Charles Shuler

Research output: Contribution to journalArticle

Abstract

Oral squamous cell carcinomas overexpress tumor-associated antigens, yet these antigens do not induce an immune-mediated anti-tumor response. The absence of an antitumor immune response may be due to poor immunogenicity of the tumor antigens or due to presence of factors that restrict immune functions. We have analyzed the expression of the tumor-associated sialyl Lewis(A) (sLe(A)) and sialyl Lewis(X) (sLE(A)) antigens, the complement restriction factors (CD59, CD46 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 complement-fixing IgM antibodies. These antigens are associated with aggressive invasive behavior, tumor progression and poor disease-free survival of patients with human carcinomas. Human oral squamous carcinoma cell lines, SCC12 and SCC71, were analyzed for the density of Sialyl Lewis antigens, CD59, CD46, CD59, Fas and Fast on the cell surface. Expression of these antigens on the cell surface was determined employing a cell-suspension ELISA with monospecific monoclonal antibodies. In both oral carcinoma cell lines, the density of expression of sLe(X) was higher A than that of sLeA 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 surface suggesting that even if host antibodies are accessible to the target antigens such as sLe(X), they could not mediate complement-dependent cytotoxicity. The SCC lines expressed very low levels of Fas and FasL indicating that there maybe a lack of these signaling molecules for apoptosis. Our data suggests that passive immunotherapy or tumor killing by antibody-complement interaction may require downregulation of complement restriction factors.

Original languageEnglish (US)
Pages (from-to)21-26
Number of pages6
JournalAnticancer Research
Volume20
Issue number1 A
StatePublished - 2000
Externally publishedYes

Fingerprint

Immunotherapy
Carcinoma
Antigens
Neoplasm Antigens
Cell Line
Squamous Cell Carcinoma
CD59 Antigens
CD46 Antigens
Apoptosis
Neoplasm Antibodies
Neoplasms
Fas Ligand Protein
Passive Immunization
Antibodies
Immunologic Factors
Surface Antigens
Disease-Free Survival
Immunoglobulin M
Suspensions
Down-Regulation

Keywords

  • Chemo-immunotherapy
  • Complement restriction factors
  • Oral carcinoma
  • Sialyl Lewis antigen

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Cell-surface expression of complement restriction factors and sialyl Lewis antigens in oral carcinoma : Relevance to chemo-immunotherapy. / Ravindranath, Narendranath M H; Nishimoto, Kevin; Chu, Kyo; Shuler, Charles.

In: Anticancer Research, Vol. 20, No. 1 A, 2000, p. 21-26.

Research output: Contribution to journalArticle

Ravindranath, Narendranath M H ; Nishimoto, Kevin ; Chu, Kyo ; Shuler, Charles. / Cell-surface expression of complement restriction factors and sialyl Lewis antigens in oral carcinoma : Relevance to chemo-immunotherapy. In: Anticancer Research. 2000 ; Vol. 20, No. 1 A. pp. 21-26.
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AB - Oral squamous cell carcinomas overexpress tumor-associated antigens, yet these antigens do not induce an immune-mediated anti-tumor response. The absence of an antitumor immune response may be due to poor immunogenicity of the tumor antigens or due to presence of factors that restrict immune functions. We have analyzed the expression of the tumor-associated sialyl Lewis(A) (sLe(A)) and sialyl Lewis(X) (sLE(A)) antigens, the complement restriction factors (CD59, CD46 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 complement-fixing IgM antibodies. These antigens are associated with aggressive invasive behavior, tumor progression and poor disease-free survival of patients with human carcinomas. Human oral squamous carcinoma cell lines, SCC12 and SCC71, were analyzed for the density of Sialyl Lewis antigens, CD59, CD46, CD59, Fas and Fast on the cell surface. Expression of these antigens on the cell surface was determined employing a cell-suspension ELISA with monospecific monoclonal antibodies. In both oral carcinoma cell lines, the density of expression of sLe(X) was higher A than that of sLeA 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 surface suggesting that even if host antibodies are accessible to the target antigens such as sLe(X), they could not mediate complement-dependent cytotoxicity. The SCC lines expressed very low levels of Fas and FasL indicating that there maybe a lack of these signaling molecules for apoptosis. Our data suggests that passive immunotherapy or tumor killing by antibody-complement interaction may require downregulation of complement restriction factors.

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