Predominant expression of B7-H1 and its immunoregulatory roles in oral squamous cell carcinoma.
We examined cell surface expression of five B7 costimulatory molecules (B7-H1, B7-DC, B7h, CD80 and CD86) in human oral squamous cell carcinoma (SCC) lines. Most human SCC cell lines expressed various levels of B7-H1 and B7-DC. Their expression was further upregulated by interferon (IFN)-gamma stimulation. Immunohistochemical staining revealed substantial and predominant expression of B7-H1 on human primary oral SCC. A murine SCC line, NR-S1, neither expressed B7-H1 nor B7-DC, but induced B7-H1 by IFN-gamma stimulation in culture and the inoculation in vivo. Although NR-S1 tumors grew progressively in immunocompetent syngeneic mice, the administration of blocking anti-B7-Hl or anti-PD-1 mAb significantly inhibited the tumor growth, suggesting the negative regulation of host immune responses by the PD-1:B7-H1 pathway. Our results demonstrate that B7-H1 is predominantly induced on oral SCC within the B7 family molecules. A successful inhibition of tumor growth by blockade of the PD-1:B7-H1 pathway may implicate a new approach for immunotherapy of oral SCC.
Tsushima
Fumihiko
F
Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
Tanaka
Kae
K
Otsuki
Noriko
N
Youngnak
Pornpan
P
Iwai
Hideyuki
H
Omura
Ken
K
Azuma
Miyuki
M
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D018122:B7-1 Antigen / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D009062:Mouth Neoplasms / Q000276:immunology*; D061027:Programmed Cell Death 1 Ligand 2 Protein
D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; C556977:PDCD1LG2 protein, human; C556978:Pdcd1lg2 protein, mouse; D061027:Programmed Cell Death 1 Ligand 2 Protein; D007371:Interferon-gamma