No abstract

Perioperative feeding with a supplemented enteral diet modulates cytokine production and enhances cell-mediated immunity and the synthesis of short half-life proteins.

Amino-biphosphonates (like pamidronate) activate human V;9/VD2 T lymphocytes and promote their cytotoxicity against multiple myeloma cells. T-cell receptor (TCR)-mediated effector functions of ;D cells are enhanced upon triggering of the activating receptor NKG2D by MICA, a stress-inducible antigen expressed by epithelial and some hematopoietic tumors, including multiple myeloma. Here we show that MICA was expressed not only by myeloma cell lines and by 6 of 10 primary multiple myeloma cells from patients but also by bone marrow plasma cells from all (six of six) patients with preneoplastic gammopathy (monoclonal gammopathy of undetermined significance, MGUS), a direct precursor of multiple myeloma. Moreover, compared with multiple myeloma plasma cells, MICA was expressed by MGUS plasma cells at significantly (P < 0.05) higher levels. MICA expressed by myeloma cell lines contributed to killing and IFN-; production by V;9/VD2 cells only upon pamidronate treatment, suggesting a dual interaction between V;9/VD2 lymphocytes and multiple myeloma plasma cells involving both TCR triggering and NKG2D-mediated signals. Finally, MICA enhanced killing of freshly derived, pamidronate-treated multiple myeloma cells from patients by ;D cells, as indicated by the significantly (P < 0.05) higher ;D cytotoxicity against MICA-positive rather than MICA-negative multiple myeloma cells. Our results indicate that MICA expressed by monoclonal plasma cells is functional and correlates with disease stages, suggesting a role for the molecule in the immune surveillance against multiple myeloma. Moreover, pamidronate-activated V;9/VD2 lymphocytes can be exploited in the immune therapy of early stages multiple myeloma and possibly of premalignant disease. (Cancer Res 2005; 65(16): 7502-8)

NK cell-mediated immune surveillance against infected DC may be effective only during early HIV infection and may not be restored by HAART.