Lymphocyte activation gene-3 induces tumor regression and antitumor immune responses.
The lymphocyte activation gene-3 (LAG-3) product is an MHC class II ligand related to CD4. We investigated whether LAG-3 could be used in vivo to stimulate MHC class II(+) antigen-presenting cells (APC), such as resident macrophages or dendritic cells known to play a crucial role in processing and presenting of antigens to the immune system. We first introduced human (h) LAG-3 or mouse LAG-3 into three types of tumor cells (MCA 205, TS / A and RENCA) to evaluate its capacity to stimulate a tumor-specific immune response in vivo. In contrast to the progressive growth of wild-type cells in syngeneic mice, LAG-3-transfected tumors completely regressed or their growth was markedly reduced. Mice were significantly to completely protected against a rechallenge with parental tumor cells. Protection induced by hLAG-3(+) tumor cells involved recruitment of a CD8(+) T cell response since nu / nu mice and CD8-depleted mice did not reject tumors, and a systemic tumor-specific CTL activity was induced. Co-administration of soluble LAG-3 with wild-type tumor cells also markedly reduced primary tumor growth. Interestingly, immunization with LAG-3(+) tumor cells or co-administration of soluble LAG-3 with irradiated wild-type tumor cells reduced the growth of pre-established tumors. We therefore suggest that LAG-3 could be used as a vaccine adjuvant for its ability to trigger APC via MHC class II molecules.
Prigent
P
P
Laboratoire d'Immunologie Cellulaire Institut Gustave-Roussy, Villejuif, France.
El Mir
S
S
Dréano
M
M
Triebel
F
F
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D015703:Antigens, CD; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006801:Humans; D008264:Macrophages / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology; D014407:Tumor Cells, Cultured; D000093322:Lymphocyte Activation Gene 3 Protein
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D008565:Membrane Proteins; D000093322:Lymphocyte Activation Gene 3 Protein