Persistence of dormant tumor cells in the bone marrow of tumor cell-vaccinated mice correlates with long-term immunological protection.

Live proliferation-competent and irradiated proliferation-incompetent L5178 murine lymphoma cells (Eb cell line) were compared for their potency to induce systemic anti-tumor immunity in syngeneic DBA/2 mice. The tumorigenic potential in vivo of live Eb cells was suppressed through local secretion of interleukin 4 (IL4) or alternatively by injection of parental cells at a site refractory to tumor growth. Inoculation of nontumorigenic doses of live Eb or Eb-IL4 cells led to long-lasting specific and systemic T-cell-mediated antitumor response requiring both CD4+ and CD8+ T lymphocytes. Irradiated cells offered only limited short-term protection, which could be marginally improved by IL4. The more effective protection offered by vaccination with live tumor cells correlated with rapid migration and persistence of tumor cells in the bone marrow of host animals after tumor cell inoculation. In contrast, irradiated Eb-lacZ cells had a short persistence. Tumor cells recovered from the bone marrow of host animals injected with live Eb-IL4 cells still expressed IL4. These observations indicate that in the course of vaccination with live Eb or Eb-IL4 cells, a fraction of these cells escaped destruction by host mechanisms and persisted in a dormant state in the bone marrow for long periods of time. Persistence of dormant tumor in the bone marrow correlated with the duration of anti-tumor immunity.