Cancer Immunology, Immunotherapy

, Volume 57, Issue 1, pp 85–95 | Cite as

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

  • David Schrama
  • Heike Voigt
  • Andreas O. Eggert
  • Rong Xiang
  • He Zhou
  • Ton N. M. Schumacher
  • Mads H. Andersen
  • Per thor Straten
  • Ralph A. Reisfeld
  • Jürgen C. Becker
Original Article

Abstract

Background

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.

Conclusion

Thus, our data demonstrate that targeted LTα promotes an accelerated immune response by enabling the priming of T cells at the tumor site.

Keywords

T cells Cytokines Tumor immunity Lymphotoxin alpha knock-out mice Antibody 

Abbreviations

APCs

Antigen presenting cells

HEV

High endothelial venules

LTα

Lymphotoxin α

LTα−/−

LTα knock-out

LTβR

LTβ receptor

sLTα

Soluble lymphotoxin α

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • David Schrama
    • 1
  • Heike Voigt
    • 1
  • Andreas O. Eggert
    • 1
  • Rong Xiang
    • 2
  • He Zhou
    • 2
  • Ton N. M. Schumacher
    • 3
  • Mads H. Andersen
    • 4
  • Per thor Straten
    • 4
  • Ralph A. Reisfeld
    • 2
  • Jürgen C. Becker
    • 1
  1. 1.Department of DermatologyJulius-Maximilians-University, University of WürzburgWürzburgGermany
  2. 2.The Scripps Research InstituteLa JollaUSA
  3. 3.Division of immunologyThe Netherlands Cancer InstituteAmsterdamThe Netherlands
  4. 4.Tumor Immunology GroupInstitute of Cancer Biology, Danish Cancer SocietyCopenhagenDenmark

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