Human inflammatory cells within the tumor microenvironment of lung tumor xenografts mediate tumor growth suppression in situ that depends on and is augmented by interleukin-12

The human tumor microenvironment includes a mixture of tumor cells, inflamm atory cells, fibroblasts, and endothelial cells, all of which are tethered to an extracellular matrix. It has been difficult to study the dynamic inte ractions of these cells in human tumors in situ for obvious ethical and log istical considerations that prohibit experimental manipulations of rumors w hile still in patients. Fresh tissue from human lung tumor biopsy implanted into SCID mice was shown to remain viable, and the histologic appearance o f the tumor microenvironment was maintained in the tumor xenografts for at least 3 months. In this study, the authors established that the inflammator y cells within human turner xenografts can suppress tumor growth, and that this suppression is a result, in part, of endogenously produced interleukin -12 (IL-12) because IL-12 neutralizing antibodies enhance the growth of the tumor xenografts. The tumor-inhibitory activity of the inflammatory leukoc ytes is also enhanced by the local and sustained. release of human recombin ant IL-12 into the tumor microenvironment from cytokine-loaded biodegradabl e microspheres. Neither the anti-IL-12 neutralizing antibody nor the delive ry of exogenous IL-12 from microspheres had any effect on tumor xenografts in the absence of the inflammatory leukocytes. In conclusion, the inflammat ory cells within the tumor microenvironment of human lung tumor xenografts are functional and can suppress tumor growth, and the dynamic effects of th e inflammatory cells can be modulated by exogenous cytokines.