Prognostic value of tumor-infiltrating dendritic cells expressing CD83 in human breast carcinomas.
DCs are the most potent antigen-presenting cells that play a major role in initiating the antitumor immune response. Although the clinical significance of TIDCs has been investigated in a variety of human cancers, few studies have focused on the in situ maturation status of DCs. We have analyzed the maturation-specific significance of TIDCs in the prognosis of patients with breast carcinoma. We evaluated 130 breast carcinomas for the presence of TIDCs using immunohistochemistry with an anti-CD1a antibody for immature DCs and an anti-CD83 antibody for mature DCs. Intratumoral expression of immunosuppressive cytokines was also examined. All samples contained CD1a(+) TIDCs, and 82 (63.1%) samples contained CD83(+) TIDCs. The number of CD83(+) TIDCs was inversely correlated with lymph node metastasis and with tissue expression of VEGF and TGF-beta, whereas the number of CD1a(+) TIDCs was not. Kaplan-Meier analysis (log rank statistics) revealed a significant association of increasing number of CD83(+) TIDCs with longer relapse-free (p = 0.002) and overall (p < 0.001) survival. Furthermore, among patients with lymph node metastasis, the survival rate of those with larger numbers of CD83(+) TIDCs was significantly better than that of patients with fewer CD83(+) TIDCs. Multivariate analysis revealed that CD83(+) TIDCs had independent prognostic relevance in breast carcinomas. The infiltration of tumors by mature DCs expressing CD83 may be of great importance in initiating the primary antitumor immune response and is confirmed as an independent, immunologic prognostic parameter for survival in patients with breast cancer.
Iwamoto
Mitsuhiko
M
Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki, Osaka, Japan.
Shinohara
Hisashi
H
Miyamoto
Akiko
A
Okuzawa
Masaaki
M
Mabuchi
Hideaki
H
Nohara
Takehiro
T
Gon
Goki
G
Toyoda
Masao
M
Tanigawa
Nobuhiko
N
D002293:Adenocarcinoma, Scirrhous / Q000737:chemistry / Q000276:immunology / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D015703:Antigens, CD; D018949:Antigens, CD1 / Q000032:analysis; D001943:Breast Neoplasms / Q000737:chemistry / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000737:chemistry / Q000276:immunology / Q000401:mortality / Q000473:pathology; D003713:Dendritic Cells / Q000737:chemistry*; D016228:Endothelial Growth Factors / Q000032:analysis; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis*; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis; D015993:Life Tables; D008207:Lymphatic Metastasis; D008222:Lymphokines / Q000032:analysis; D008562:Membrane Glycoproteins / Q000032:analysis*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D009418:S100 Proteins / Q000032:analysis; D016019:Survival Analysis; D016212:Transforming Growth Factor beta / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000097802:CD83 Antigen
D015703:Antigens, CD; D018949:Antigens, CD1; D016228:Endothelial Growth Factors; D007136:Immunoglobulins; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D009418:S100 Proteins; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000097802:CD83 Antigen; C419393:CD1a antigen