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Red Cell Disorders

Human oesophageal squamous carcinoma produces a partially purified, soluble, low molecular weight immunosuppressive factor which inhibits activated lymphocytes in vim0 and in vivo (O’Mahoney et a1 (1993) Journal of Immunology 151: 4847-56). It is well recognised that advanced solid malignancy is often associated with bone marrow suppression. To further investigate this poorly understood phenomenon, and in particular the role of humoral tumourderived factors, we studied the effects of the immunosuppressive factor on haemopoietic progenitors using different human and murine experimental models. The murine multipotent stem cell line “FDCP-Mix” when cultured in the presence of Interleukin-3 remains primitive; however, when cultured in G-CSF, GM-CSF, IL-3 and foetal calf serum the cells differentiate. The immunosuppressive factor was found to potently inhibit the FDCPMix cells in differentiate conditions in a dose-dependent manner (80% suppression at max. concentration), but had no inhibitoly effect on the cells when they were maintained as primitive multipotent stem cells. Similarly, in semi-solid media colony formation by committed myeloid progenitors, (purified from whole murine marrow by elutriation) was potently inhibited (90% at max. concentration) in a dose-dependent manner by the immunosuppressive factor while colony formation by murine multipotent stem cells was unaffected by the immunosuppressive factor. Culture of human CD34 positive cord blood cells in methylcellulose showed potent inhibition of BFU-E (95% at max. concentration) and GM colony formation (80% at max. concentration) in a dose dependent manner. These data support the observation that solid malignancy is associated with marrow suppression and indicate that in human oesophageal squamous carcinoma a low molecular weight soluble mediator, the immunosuppressive factor, contributes significantly to this effect.