Prognostic value of tumor‐infiltrating dendritic cells expressing CD83 in human breast carcinomas

Abstract

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-␤, 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 relapsefree (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.

CD83+ dendritic cells and Foxp3+ regulatory T cells in primary lesions and regional lymph nodes are inversely correlated with prognosis of gastric cancer

“…DCs in various cancer tissues is associated with poor prognosis [7][8][9][10][11][12]. However, regarding DC activation, it is not clear what kind of immune responses occur in the draining lymph nodes.…”

Dendritic Cells and Tumor Microenvironment: A Dangerous Liaison

“…Mature MDCs are potent inducers of T helper 1 (T H 1)-type immune responses and also are considered as powerful initiators of tumor associated antigen (TAA)-specific immunity. However, the appearance of functional competent myeloid mDCs inside the tumor is rare as described for human ovarian (Zou, et al 2001), breast (Bell, et al 1999,Iwamoto, et al 2003, prostate (Troy, et al 1998a) and renalcell cancers (Troy, et al 1998b). Multiple factors may be responsible for this phenomenon, such as defective DC recruitment, differentiation, maturation, and survival.…”

The ‘kiss of death’ by dendritic cells to cancer cells

“…7,8 Indeed, the presence of DCs in human carcinomas has been largely documented 9 and certain studies associated the quality and/or quantity of tumor-infiltrating DCs to a favorable prognosis for the patient. [10][11][12][13] It is traditionally believed that apoptotic bodies or necrotic debris are generated as a result of direct killing of tumor cells by NK cells and CTLs. 1 However, there is growing evidence that conventional DCs or certain DC subsets are endowed with a direct tumoricidal property by delivering cell death signals to pre-malignant/malignant cells, and also by providing signals required for their own maturation into immunostimulatory APCs.…”