Altered surface expression patterns of circulating monocytes in cancer patients: impaired capacity of T-cell stimulation?

Dear Editor,

In their Letter, Luczynski et al. report a down-regulated expression of HLA-DR and CD86/B7-2 on CD14⁺ peripheral blood monocytes of children suffering from various cancers compared with a group of children with benign diseases. These observations are in line with our flow cytometry results revealing a reduced monocyte surface expression of these markers in melanoma patients compared with healthy volunteers [2]. Moreover, a decreased expression of CD80/B7-1 was detected on monocytes from children with cancer, which was not seen in melanoma patients. No significant changes were found in the expression of the adhesion molecule CD54 in children with cancer, whereas melanoma patients presented a strongly decreased expression of the adhesion molecule CD11c.

The study group of Luczynski et al. additionally comprised children with severe or therapy-resistant infections. Interestingly, monocytes derived from these children showed the strongest reduction in HLA-DR cell surface expression. This observation confirms our previous report of a significantly reduced HLA-DR expression on monocytes from patients with severe septicemic infections associated with decreased serum concentrations of soluble HLA-DR molecules in these patients [1].

The similar but not identical expression patterns observed in monocytes from melanoma patients as well as from children with malignant diseases imply a reduced antigen presentation capacity of these cells. As proposed by Luczynski et al., this might be associated with an impaired T-cell stimulation capacity, enabling tumor cells to escape from immune surveillance. To test this hypothesis, we recently measured the in vitro proliferation of peripheral blood mononuclear cells toward different recall antigens and mitogens in ten melanoma patients versus five healthy controls. With regard to recall antigens we observed a slight reduction of proliferation in early stage, nonmetastasized patients in comparison to healthy controls, whereas a strongly impaired proliferation could be detected in patients with distant metastases. In contrast, the response capacity toward mitogens was similar in all three groups. These preliminary results point to a stage-dependent decrease in antigen-specific T-cell proliferation that might be caused by the observed stage-dependent down-regulation of HLA-DR and costimulatory molecules, respectively, on peripheral blood monocytes of melanoma patients.