Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Schrama, D; Voigt, H; Eggert, AO; Xiang, R; Zhou, H; Schumacher, TNM; Andersen, MH; Straten, PT; Reisfeld, RA; Becker, JC.
Immunological tumor destruction in a murine melanoma model by targeted LT alpha independent of secondary lymphoid tissue
CANCER IMMUNOL IMMUNOTHER. 2008; 57(1): 85-95.
Doi: 10.1007/s00262-007-0352-x
Web of Science
PubMed
FullText
FullText_MUG
Google Scholar
- Leading authors Med Uni Graz
- Schrama David
- Co-authors Med Uni Graz
- Becker Jürgen Christian
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- 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. METHODS AND 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. CONCLUSION: Thus, our data demonstrate that targeted LTalpha promotes an accelerated immune response by enabling the priming of T cells at the tumor site.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Gangliosides - immunology
- Humans -
- Immunohistochemistry -
- Lymphocyte Activation - immunology
- Lymphocytes, Tumor-Infiltrating -
- Lymphoid Tissue - cytology Lymphoid Tissue - immunology
- Lymphotoxin-alpha - immunology Lymphotoxin-alpha - therapeutic use
- Melanoma, Experimental - immunology Melanoma, Experimental - therapy
- Mice -
- Mice, Inbred C57BL -
- Mice, Knockout -
- Recombinant Fusion Proteins - immunology Recombinant Fusion Proteins - therapeutic use
- T-Lymphocytes - immunology
- Find related publications in this database (Keywords)
- T cells
- cytokines
- tumor immunity
- lymphotoxin alpha knock-out mice
- antibody