Studies on lymphatic metastasis. I. Primary immunoregulatory role of regional lymph nodes in the establishment of lymphatic metastases.

The growth of syngeneic ascites MM48 tumor cells implanted in a hind footpad of a C3H/He mouse slowed at 10-12 days after tumor implantation. At that time, no killer activity was detected in all lymphoid organs examined, including regional lymph node. However, positive immunoregulatory activity, i.e., killer-augmenting activity, which was assessed by cytotoxicity assay with tumor-specific immune cytotoxic T-cells, was detected primarily in the regional lymph node. In contrast, local preimmunization with larger doses of irradiated tumor cells enhanced growth of subsequently challenged tumor and lymphatic metastasis. In the regional node of preimmunized tumor bearer, negative immunoregulatory activity, i.e., killer-suppressing activity, was induced. Both immunoregulatory activities were tumor specific and resided in Lyt-1+ T-cells. Tumor-specific immunoregulatory activity seemed to be related to tumor dose used for challenge, whether positive or negative immunoregulatory activity was induced. Lymphatic metastases examined by bioassay and histologic examination were evaluated with reference to immunoregulatory activity that appeared in the regional lymph node during tumor development. The incidence of tumor detection in the node by bioassay was decreased when killer-augmenting activity was present there. Proliferation of metastatic tumor cells judged by microscopic observation was in parallel with suppressor activity generated in the node.