Development of antitumor reactivity in regional draining lymph nodes from tumor-immunized and tumor-bearing murine hosts.

With use of the weakly immunogenic MCA 105 tumor of the C57BL/6 mouse, the antitumor reactivity of lymphoid cells derived from the regional draining lymph nodes (RLN) of tumor-immunized and tumor-bearing mice was examined. Mice were immunized with an inoculation of viable tumor admixed with Corynebacterium parvum. Excision of tumor immunization sites within 4 days abrogated the development of systemic immunity to reject a tumor challenge. However, excision of the immunization site on day 6 did not interfere with the development of systemic antitumor immunity. In subsequent experiments, tumor immunization sites were excised on day 6 in all mice and the RLN either left intact or excised on day 6 or day 14. The development of systemic tumor immunity was severely impaired if RLN were excised on day 6, indicating the pivotal role of the RLN. Excision of the RLN on day 14 had no impact on the development of systemic immunity, thus indicating that the requirement for the RLN was time dependent. In mice bearing progressively growing tumors, lymphoid cells derived from RLN were examined for therapeutic efficacy in adoptive immunotherapy experiments. Although fresh RLN cells harvested 6 and 14 days after tumor inoculation did not demonstrate inherent therapeutic efficacy, after in vitro sensitization with irradiated tumor cells and interleukin-2, these RLN cells acquired significant antitumor activity in adoptive immunotherapy experiments. These data indicate that RLN are essential in the development of tumor immunity and may be used as a source of therapeutic effector cells for adoptive immunotherapy.