Abstract

Immune aberration in cancer patients can be at least partly ascribed to an accumulation of immature myeloid cells and monocytes/macrophages with immunosuppressive functions. Mice implanted with Lewis lung carcinoma 2 (LL/2) cells show marked splenomegaly as the tumors progress, and this condition is accompanied by impaired T cell activities. We characterized the cells that accumulated in the spleens of LL/2 tumor-bearing mice and attempted to restore the normal cell population by employing interleukin-2 (IL-2). Flow cytometric analysis revealed that the cells expressing Mac1, B7, NK-K1, Gra-1, and MHC class II antigens on their surfaces drastically decreased in number when LL/2 had been engineered to produce IL-2. IL-2 also restored the concanavalin A (ConA)-mediated proliferative response and IL-2 production of the spleen cells. The in vivo growth of IL-2-producing tumors was significantly slower than that of parental LL/2 cells. Therefore, local IL-2 production may reverse systemic immune abnormality by stopping myeloid cell accumulation.

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