In fact, leukopenia induced by gamma-irradiation of recipient mice or injection into interferon gamma (IFN-gamma) gene knockout (GKO) mice resulted in reduced mouse survival and an increased number of lung metastases.
In the melanoma model, intratumoral injection of pIL-2, but not rhIL-2, increased the number of activated CD8(+) T cells (IFN-γ(+)) in the spleen, reduced lung metastasis and prolonged the survival of treated mice.
The combined analysis of these approaches allowed us to establish a hierarchy in which patrolling monocytes, making IL15 in response to primary tumors, activate NK cells and IFNγ production that then inhibit lung metastasis formation.