Clinical importance of B7-H3 expression in human pancreatic cancer.
BACKGROUND
B7-H3 is a new member of the B7 ligand family and regulates T-cell responses in various conditions. However, the role of B7-H3 in tumour immunity is largely unknown. The purpose of this study was to evaluate the clinical significance of B7-H3 expression in human pancreatic cancer and the therapeutic potential for cancer immunotherapy.


METHODS
We investigated B7-H3 expression in 59 patients with pancreatic cancer by immunohistochemistry and real-time PCR. Furthermore, we examined the anti-tumour effect of B7-H3-blocking monoclonal antibody in vivo in a murine pancreatic cancer model.


RESULTS
Tumour-related B7-H3 expression was abundant in most human pancreatic cancer tissues and was significantly higher compared with that in non-cancer tissue or normal pancreas. Moreover, its expression was significantly more intense in cases with lymph node metastasis and advanced pathological stage. B7-H3 blockade promoted CD8(+) T-cell infiltration into the tumour and induced a substantial anti-tumour effect on murine pancreatic cancer. In addition, the combination of gemcitabine with B7-H3 blockade showed a synergistic anti-tumour effect without overt toxicity.


CONCLUSIONS
Our data show for the first time that B7-H3 may have a critical role in pancreatic cancer and provide the rationale for developing a novel cancer immunotherapy against this fatal disease.
Department of Surgery, Nara Medical University, Nara 634-8522, Japan.
I
I
Yamato
M
M
Sho
T
T
Nomi
T
T
Akahori
K
K
Shimada
K
K
Hotta
H
H
Kanehiro
N
N
Konishi
H
H
Yagita
Y
Y
Nakajima
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology*; D060887:B7 Antigens; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D060887:B7 Antigens; D014408:Biomarkers, Tumor; C423237:CD276 protein, human; D011971:Receptors, Immunologic