Mature dendritic cells make clusters with T cells in the invasive margin of colorectal carcinoma

Abstract

Dendritic cells (DCs) take up tumour-specific antigen and migrate to regional lymph nodes to generate anti-tumour immunity. Although DC infiltration within human tumour tissue has been reported, the subset distribution has not been fully investigated. This study used immunohistochemistry to investigate DC subset distribution in colorectal adenocarcinoma. DCs expressing CD83, which are considered to be mature DCs, were present mainly in the invasive margin of cancer stroma. CD83(+) DCs in the invasive margin formed clusters with lymphocytes, the majority of which were CD45RO(+) T cells. The number of CD4(+) T cells was greater than that of CD8(+) T cells in these DC-lymphocyte clusters. The elongated cytoplasmic processes of CD83(+) DCs engulfed CD4(+) T cells. DCs that express CD1a were located throughout tumour tissue. Although the number of CD1a(+) DCs was almost the same as that of CD83(+) DCs in the invasive margin of cancer stroma, CD1a(+) DCs were mostly scattered and rarely formed clusters with lymphocytes. DCs that expressed both CD1a and CD83 were rare. Moreover, about 20% of lymphocytes in DC-lymphocyte clusters were positive for Ki-67, and CD83(+) DCs were attached to Ki-67(+) cells. CD83(+) DCs were also present in T-cell areas that had a distinctive structure involving the presence of B-cell lymphoid follicles. These results suggest that in the invasive margin of the colorectal cancer stroma, mature CD83(+) DCs form clusters with T cells to promote T-cell activation for the generation of tumour-specific immunity.

Glycosylation-Dependent Interactions of C-Type Lectin DC-SIGN with Colorectal Tumor-Associated Lewis Glycans Impair the Function and Differentiation of Monocyte-Derived Dendritic Cells

“…Possibly, expression of DC-SIGN specifically on immature DCs enables these cells but not mature DCs to associate with colorectal tumors. The presence of immature DCs with proliferating CD4 and CD8 T cells has been reported (27,29). The numbers of these mature DCs and tumor-infiltrating lymphocytes correlate with a metastasis-free condition and the survival of colorectal cancer patients (30).…”

“…6). Previously, it was reported that immature DCs are present intratumorally, whereas mature DCs are located peritumorally (27,28). Possibly, expression of DC-SIGN specifically on immature DCs enables these cells but not mature DCs to associate with colorectal tumors.…”

Invasive front of colorectal cancer: Dynamic interface ofpro-/anti-tumor factors

“…Evidence is accumulating which suggests that the presence of dendritic cells may be of significant benefit to patients with colorectal cancer [82] . Using immunohistochemistry for CD83, Suzuki et al [83] described the presence of mature dendritic cells at the invasive margin of cancer stroma and demonstrated by light and electron microscopy their formation into clusters with lymphocytes, the majority of which were CD45RO+ T cells. They conclude that mature CD83+ dendritic cells at the invasive margin promote T-cell activation for the generation of tumor specific immunity.…”

The Janus face of dendritic cells in cancer

“…The location of the TIDC infiltrate mattered for the prognosis. Bell et al in breast cancer and Suzuki et al in colorectal carcinoma showed that mature DCs make clusters with T lymphocytes in the margin of tumors, whereas immature DCs invade the epithelium (Bell et al, 1999;Suzuki et al, 2002). In contrast, the opposite pattern was associated with a dismal prognosis in colorectal tumors (Sandel et al, 2005).…”