Dendritic Cell Infiltration in Colon Cancer

Abstract

We quantitatively evaluated dendritic cell (DC) infiltration in primary colorectal cancers from 44 patients and metastatic colorectal tumors from 13 patients using immunohistochemistry for the DC marker CD83, HLA-DR, and the DC activation molecules CD40 and CD86. Nearly all CD83+ cells were also HLA-DR+, CD40+, and CD86+, indicating that the DCs that infiltrate colon cancer in vivo express the activation and costimulatory molecules associated with a mature DC phenotype. The density of DCs in colorectal cancer primaries was three times lower than that seen in normal colonic mucosa (0.29 versus 0.84 CD83+ cells/ high-power field (hpf), p < 0.001). Dendritic cells were rarely observed in metastatic tumors: DC density in metastases was sixfold lower than in colorectal primary tumors (0.05 versus 0.29 CD83+ cells/hpf, p < 0.001). Because cytokines have been shown, in vitro, to exert potent effects on DCs, we also evaluated the relationship between intratumor DC density and the expression of cytokines by tumor-infiltrating lymphocytes (TILs) and tumor cells. Expression of interleukin-10 and transforming growth factor beta by either TIL or tumor cells was not associated with decreased DC density or decreased expression of CD40 or CD86 on DCs. Tumor expression of vascular endothelial growth factor was associated with a more than twofold increase in DC density (p = 0.01). Patients who had a high proportion of TILs expressing tumor necrosis factor (TNF) had a greater intratumor mature DC density than patients with a low proportion of TNF + TIL (0.54 versus 0.21 CD83+ cells/hpf, p < 0.01).

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).…”

Role of infiltrated leucocytes in tumour growth and spread

“…Dendritic cells (DCs) also play an important role in both the activation of antigen-specific immunity and the maintenance of tolerance, providing a link between innate and adaptive immunity. Several clinical studies have reported the presence of DC within human tumours such as the stomach, colon, prostate, kidney, thyroid, breast and melanoma (Tsujitani et al, 1990;Enk et al, 1997;Troy et al, 1998;Bell et al, 1999;Lespagnard et al, 1999;Schwaab et al, 1999Schwaab et al, , 2001Scarpino et al, 2000). However, the effect of such an infiltration in tumour progression is still not clear.…”

Prognostic Value of the Tumour-Infiltrating Dendritic Cells in Colorectal Cancer: A Systematic Review

“…Two other studies recognised DCs by their distribution pattern and morphology (Sandel et al, 2005;Dadabayev et al, 2004). DCs were identifi ed as the HLA-DR ( ϩ )/CD83 ( ϩ ) positive cells by Schwaab et al (2001). Cells stained with S-100, HLA-DR, CD1a or CD83 were considered to be DCs by Gulubova et al (2012).…”

“…Full-text review of these resulted in four exclusions that included three review papers and one study investigating the DCs at the invasive margin of CRC but not associating with outcomes. Eight studies were judged to be eligible in this review, all of which were cohort studies (evidence grade C based on the SIGN grading system) (Ambe et al, 1989;Schwaab et al, 2001;Gulubova et al, 2012;Nagorsen et al, 2007;Sandel et al, 2005;Nakayama et al, 2003;Dadabayev et al, 2004;Liska et al, 2012). A total of 651 specimens, all diagnosed with CRC at all stages, were included.…”

“…DC-SIGN is expressed by immature DCs, whereas DC-LAMP is present on mature DCs. Also Schwaab et al (2001) focussed not only on the presence of mature TIDCs, but also on their activation status staining for CD40 surface marker.…”