Fas ligand expression in human pancreatic cancer.
Tumor cells escape immunologic rejection through diverse mechanisms. Fas and its ligand represent one such mechanism. Recently we reported that pancreatic cancer cell lines express Fas-ligand and kill lymphoid cells by Fas-mediated apoptosis in vitro. This study was designed to determine whether human pancreatic tumors express Fas-ligand in vivo, as a potential mediator of counterattacking the host immune cells, and to determine if Fas-ligand expression correlates with clinicopathologic characteristics and patient survival. Fas-ligand expression in 45 primary pancreatic ductal cancers and two hepatic metastases was determined using immunohistochemistry. Apoptotic cells within the tumor were assessed by immunohistochemistry for the presence of single stranded DNA. Immunohistochemistry showed that 37 (82%) of the primary tumors and both of the hepatic metastases expressed Fas-ligand. Tumor infiltrating lymphoid cells were frequently apoptotic, but the cancer cells were rarely apoptotic. Patients with Fas-ligand-positive tumor had significantly shorter survival times than Fas-ligand-negative. A multivariate analysis indicated that Fas-ligand expression and the histologic margin status were significant prognostic factors. These results suggest that the expression of Fas-ligand in human pancreatic cancers and the induction of apoptosis in the infiltrating lymphoid cells may be required to counterattack the host cytotoxic T-lymphocytic and natural killer cellular responses.
Ohta
Tetsuo
T
Department of Surgical Oncology, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-0934, Japan. ohtat@surg2.m.kanazawa-u.ac.jp
Elnemr
Ayman
A
Kitagawa
Hirohisa
H
Kayahara
Masato
M
Takamura
Hiroyuki
H
Fujimura
Takashi
T
Nishimura
Gen-Ichi
G
Shimizu
Koichi
K
Yi
Shuang-Qin
SQ
Miwa
Koichi
K
D017209:Apoptosis; D021441:Carcinoma, Pancreatic Ductal / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004277:DNA, Single-Stranded / Q000235:genetics / Q000378:metabolism; D053222:Fas Ligand Protein; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000556:secondary; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic
D004277:DNA, Single-Stranded; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins