Then, 50 to 70 l (1 l per 1 million of PBMCs) of anti-CD14 magnetic beads (Miltenyi Biotec, Bergisch Gladbach, Germany) was added to the PBMC pellet

Then, 50 to 70 l (1 l per 1 million of PBMCs) of anti-CD14 magnetic beads (Miltenyi Biotec, Bergisch Gladbach, Germany) was added to the PBMC pellet. were significantly lower than those detected in CRC tumors. However, HLA class II antigen staining was weakly detected only in 5.4% of 37 normal mucosa tissues. HLA class II antigen expression was associated with a favorable clinical course of the disease. stimulation with interferon gamma (IFN) induced HLA class II antigen expression on two of the four CRC cell lines tested. HLA class II antigen expression on CRC cells triggered interleukin-1 (IL-1) production by resting monocytes. HLA class II antigen expression in CRC tumors is a favorable prognostic marker. This association may reflect stimulation of IL-1 production by monocytes. Introduction According to genetic profiles, colorectal carcinoma (CRC) tumors are classified in two groups. About 75% of patients have CRC tumors of sporadic origin, with no clear evidence of having inherited the disease. In contrast, about 25% of patients with CRC tumors are likely to have a hereditary contribution. The cause of an inherited CRC tumor risk involves defects in the DNA mismatched repair (MMR) system leading to an increased possibility of colorectal cells to acquire mutations [1]. MMR deficiency condition seems to be associated with Thevetiaflavone high density of lymphocyte infiltration, reduced invasiveness, and improved survival [2]. Besides being expressed on antigen presenting cells, B lymphocytes, and activated T lymphocytes, HLA class II antigens are also expressed in a variety of malignant tumors of different embryological origin. The frequency of expression reaches 74.5% in medullary breast carcinoma, 17.7% in ductal breast carcinoma [3], 100% in renal cell carcinoma [4], and 60% in primary melanomas [5]. In some Thevetiaflavone malignancies such as melanomas [6] and osteogenic sarcoma [7], HLA class II antigen expression is associated with poor prognosis, while it is associated with favorable prognosis in cervical carcinoma [8] and in squamous cell carcinoma of the larynx [9]. Limited information is available about HLA class II antigen expression in CRC tumors and its clinical significance. To the best of our knowledge, a total of only two large studies involving more than 300 patients have been accomplished so far. The first study included 357 patients with micro-satellite stable CRC tumors [10]; the second study involved 1016 CRC patients with rectal carcinoma [11]. The average frequency of HLA class II antigen expression has been found to be 38% with ranges from 21% to 55% [12]. Conflicting information is available about the clinical significance of HLA class II antigen expression in CRC tumors. HLA class II antigen expression in CRC tumors has been reported to be associated with favorable prognosis by Lovig et al., Matsushita et al., and Morita et al. [10,13C15] and in a population of patients with rectal carcinoma by de Bruin et al. [11] but also with irrelevant prognosis because HLA class II antigen expression in CRC cells was not associated with the clinical course of the disease by Moller et al., Mulder et al., Diederichsen et al., and Momburg et al. [16C19]. The reason(s) for these conflicting results is (are) not known. In human, presence of Thevetiaflavone inflammatory infiltrate, in CRC Rabbit Polyclonal to Cox2 tumors, has been associated with favorable prognosis [2,20]. HLA class II antigens play a pivotal role in stimulating an inflammatory response against pathogen and tumor antigens. They are not expressed in normal colonic epithelium but could be detected in CRC cells. Furthermore, HLA class II antigen expression in colonic epithelial and CRC cells is inducible on stimulation with interferon gamma (IFN) [21]. These data suggest that HLA class II antigen expression in the CRC tumors may result from the activity of pro-inflammatory cytokines and may be associated with immunostimulation. Information about HLA class II antigen expression in CRC tumors and its clinical significance may contribute to our understanding of the role of these molecules in the interactions of CRC tumors with the host’s immune system and to the design of strategies to modulate these interactions. Therefore, in the present study, we have determined the frequency of HLA class II antigen expression in about 1000 CRC tumors, using two tissue microarrays (TMAs) independently constructed at two medical centers. Furthermore, we have analyzed the association of HLA class II antigen expression in CRC tumors with their histopathologic characteristics and the clinical characteristics of the disease. Lastly, we have investigated the potential role of pro-inflammatory cytokines in the functional properties of HLA class II antigens expressed by.