Immunological tumor destruction in a murine melanoma model by targeted LT alpha independent of secondary lymphoid tissue

Blackground We previously demonstrated that targeting lymphotoxin alpha (LT alpha) to the tumor evokes its immunological destruction in a syngeneic B16 melanoma model. Since treatment was associated with the induction of peritumoral tertiary lymphoid tissue, we speculated that the induced immune response was initiated at the tumor site. Methods and results In order to directly test this notion, we analyzed the efficacy of tumor targeted LT alpha in LT alpha knock-out (LT alpha(-/-)) mice which lack peripheral lymph nodes. To this end, we demonstrate that tumor-targeted LT alpha mediates the induction of specific T-cell responses even in the absence of secondary lymphoid organs. In addition, this effect is accompanied by the initiation of tertiary lymphoid tissue at the tumor site in which B and T lymphocytes are compartmentalized in defined areas and which harbor expanded numbers of tumor specific T cells as demonstrated by in situ TRP-2/K-b tetramer staining. Mechanistically, targeted LT alpha therapy seems to induce changes at the tumor site which allows a coordinated interaction of immune competent cells triggering the induction of tertiary lymphoid tissue. Conclusion Thus, our data demonstrate that targeted LT alpha promotes an accelerated immune response by enabling the priming of T cells at the tumor site.