Immunological tumor destruction in a murine melanoma model by targeted LTα independent of secondary lymphoid tissue
We previously demonstrated that targeting lymphotoxin α (LTα) 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 LTα in LTα knock-out (LTα−/−) mice which lack peripheral lymph nodes. To this end, we demonstrate that tumor-targeted LTα 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/Kb tetramer staining. Mechanistically, targeted LTα 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.
Thus, our data demonstrate that targeted LTα promotes an accelerated immune response by enabling the priming of T cells at the tumor site.
KeywordsT cells Cytokines Tumor immunity Lymphotoxin alpha knock-out mice Antibody
Antigen presenting cells
High endothelial venules
Soluble lymphotoxin α
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