Cyclophosphamide-dependent lymph node modification in lymph node metastasis of MM48 tumor cells in syngeneic mice

We investigated the role of immunosuppressive activity induced in the regional lymph nodes (RLN, popliteal lymph nodes) in the establishment of lymph node metastasis by cyclophosphamide (CY) administration. The CY treatment led to the elimination of suppressive activity with the appearance of positive immune responses, and the inhibition of lymph node metastasis of MM48 tumor cells. In CY-treated mice, the removal of RLN together with the primary tumor lowered the survival rate compared with the mice in which the RLN remained intact. During 4 days after primary tumor resection, the proliferation of tumor cells in the RLN was significantly decreased in CY-treated mice. These results suggested that the induction of suppressive activity in the lymph node is closely associated with the establishment of lymph node metastasis.