Expression of the costimulatory molecule B7-H3 is associated with prolonged survival in human pancreatic cancer.
BACKGROUND
Costimulatory signaling has been implicated as a potential regulator of antitumor immunity in various human cancers. In contrast to the negative prognostic value of aberrant B7-H1 expression by pancreatic cancer cells, the role of B7-H3 is still unknown. Therefore, we investigated the expression pattern and clinical significance of B7-H3 expression in human pancreatic cancer.


METHODS
B7-H3 expression was evaluated by immunohistochemistry in 68 patients with pancreatic cancer who underwent surgical tumor resection. Expression data was correlated with clinicopathologic features and with the number of tumor-infiltrating T cells.


RESULTS
B7-H3 expression was significantly upregulated in pancreatic cancer compared to normal pancreas (p < 0.05). In 60 of 68 examined tumors B7-H3 protein was detectable in pancreatic cancer cells. Patients with high tumor B7-H3 levels had a significantly better postoperative prognosis than patients with low tumor B7-H3 levels (p = 0.0067). Furthermore, tumor B7-H3 expression significantly correlated with the number of tumor-infiltrating CD8+ T cells (p = 0.018).


CONCLUSIONS
We demonstrate for the first time that B7-H3 is abundantly expressed in pancreatic cancer and that tumor-associated B7-H3 expression significantly correlates with prolonged postoperative survival. Our findings suggest that B7-H3 might play an important role as a potential stimulator of antitumor immune response in pancreatic cancer.
Loos
Martin
M
Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str 22, 81675 Munich, Germany. loos@chir.med.tu-muenchen.de
Hedderich
Dennis M
DM
Ottenhausen
Malte
M
Giese
Nathalia A
NA
Laschinger
Melanie
M
Esposito
Irene
I
Kleeff
Jörg
J
Friess
Helmut
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D060887:B7 Antigens; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000401:mortality*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000401:mortality*; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis; D014407:Tumor Cells, Cultured; D055815:Young Adult
D015703:Antigens, CD; D060887:B7 Antigens; C423237:CD276 protein, human; D011971:Receptors, Immunologic; D007371:Interferon-gamma