Tumor-draining lymph node (TDLN) ablation is routinely performed in the management of
cancer; nevertheless, its usefulness is at present a matter of debate. TDLN are central sites where T cell priming to
tumor antigens and onset of the antitumor immune response occur. However,
tumor-induced immunosuppression has been demonstrated at TDLN, leading to downregulation of antitumor reaction and tolerance induction. Tolerance in turn is a main impairment for
immunotherapy trials. We used a murine immunogenic
fibrosarcoma that evolves to a tolerogenic state, to study the cellular and molecular mechanisms underlying tolerance induction at the level of TDLN and to design an appropriate
immunotherapy. We determined that following a transient activation, the established
tumor induces signs of immunosuppression at TDLN that coexist with local and systemic evidences of antitumor response. Therefore, we evaluated the feasibility of removing TDLN in order to eliminate a focus of immunosuppression and favor
tumor rejection; but instead, a marked exacerbation of
tumor growth was induced. Combining TDLN ablation with the in vivo depletion of regulatory cells by low-dose
cyclophosphamide and the restoring of the TDLN-derived cells into the donor mouse by adoptive transference, resulted in lowered
tumor growth, enhanced survival and a considerable degree of
tumor regression. Our results demonstrate that important antitumor elements can be eliminated by
lymphadenectomy and proved that the concurrent administration of low-dose
chemotherapy along with the reinoculation of autologous cytotoxic cells provides protection. We suggest that this protocol may be useful, especially in the cases where
lymphadenectomy is mandatory.