Targeting of lymphotoxin-alpha to the tumor elicits an efficient immune response associated with induction of peripheral lymphoid-like tissue

Immunity. 2001 Feb;14(2):111-21. doi: 10.1016/s1074-7613(01)00094-2.


A recombinant antibody-lymphotoxin-alpha fusion protein induced an adaptive immune response protecting mice from melanoma. Importantly, this fusion protein elicited the formation of a lymphoid-like tissue in the tumor microenvironment containing L-selectin+ T cells and MHC class II+ antigen-presenting cells, as well as B and T cell aggregates. Furthermore, PNAd+/TCA4+ high endothelial venules were observed within the tumor, suggesting entry channels for naive T cell infiltrates. Over the course of therapy, a marked clonal expansion of certain TCR specificities occurred among tumor-infiltrating lymphocytes that displayed reactivity against melanoma cells and the TRP-2(180-188) peptide. Consequently, naive T cells may have been recruited to as well as primed and expanded in the lymphoid-like tissue induced by the lymphotoxin-alpha fusion protein at the tumor site.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Endothelium, Lymphatic / immunology
  • Endothelium, Lymphatic / pathology
  • Humans
  • Immunotoxins / therapeutic use*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / secondary
  • Lung Neoplasms / therapy
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / pathology
  • Lymphotoxin-alpha / therapeutic use*
  • Melanoma, Experimental / immunology*
  • Melanoma, Experimental / pathology
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron
  • Neoplasm Transplantation
  • Neoplasms, Connective Tissue / immunology
  • Neoplasms, Connective Tissue / pathology
  • Neoplasms, Connective Tissue / therapy
  • Recombinant Fusion Proteins / therapeutic use
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology
  • Transplantation, Isogeneic


  • Antibodies, Monoclonal
  • Immunotoxins
  • Lymphotoxin-alpha
  • Recombinant Fusion Proteins