title: Immunological tumor destruction in a murine melanoma model by targeted LTalpha independent of secondary lymphoid tissue.
abstract: BACKGROUND
  We previously demonstrated that targeting lymphotoxin alpha (LTalpha) 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.
  
  
  RESULTS
  In order to directly test this notion, we analyzed the efficacy of tumor targeted LTalpha in LTalpha knock-out (LTalpha(-/-)) mice which lack peripheral lymph nodes. To this end, we demonstrate that tumor-targeted LTalpha 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 LTalpha 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.
  
  
  CONCLUSIONS
  Thus, our data demonstrate that targeted LTalpha promotes an accelerated immune response by enabling the priming of T cells at the tumor site.
authors.affiliation: Department of Dermatology, Julius-Maximilians-University, University of Würzburg, Josef-Schneider-Str. 2, Buildg. D8, 97080, Würzburg, Germany. Schrama_D@klinik.uni-wuerzburg.de
authors.forename: David
authors.initials: D
authors.lastname: Schrama
authors.forename: Heike
authors.initials: H
authors.lastname: Voigt
authors.forename: Andreas O
authors.initials: AO
authors.lastname: Eggert
authors.forename: Rong
authors.initials: R
authors.lastname: Xiang
authors.forename: He
authors.initials: H
authors.lastname: Zhou
authors.forename: Ton N M
authors.initials: TN
authors.lastname: Schumacher
authors.forename: Mads H
authors.initials: MH
authors.lastname: Andersen
authors.forename: Per
authors.initials: P
authors.lastname: thor Straten
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Reisfeld
authors.forename: Jürgen C
authors.initials: JC
authors.lastname: Becker
mesh_terms: D000818:Animals; D005732:Gangliosides / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology*; D008233:Lymphotoxin-alpha / Q000276:immunology* / Q000627:therapeutic use*; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D005732:Gangliosides; D008233:Lymphotoxin-alpha; D011993:Recombinant Fusion Proteins; C025447:sialogangliosides