Limitations of bystander killing in Th1/M1 immune responses against a secreted tumor antigen.
T-cell recognition of tumor antigens presented on tumor-infiltrating macrophages (TAMs) induces a tumoricidal M1-like phenotype. Resultant indirect immune responses could eliminate not only antigen secreting (AgPOS), but also antigen negative (AgNEG) tumor cells via bystander killing. Such broad-spectrum response could eliminate antigenically heterogeneous tumors. Using anin vivomodel of CD4+T-cell mediated immunity against MHC II negative myeloma cells, bystander killing of AgNEGcells was ineffective due to strict spatial constraints of Th1-induced TAM cytotoxicity.
Centre for Immune Regulation; Institute of Immunology; University of Oslo and Oslo University Hospital ; Oslo, Norway.
Anders Aune
AA
Tveita
Centre for Immune Regulation; Institute of Immunology; University of Oslo and Oslo University Hospital ; Oslo, Norway.
Ole Audun
OA
Haabeth
Centre for Immune Regulation; Institute of Immunology; University of Oslo and Oslo University Hospital ; Oslo, Norway ; KG Jebsen Centre for Research on Influenza Vaccines; Institute of Immunology; University of Oslo and Oslo University Hospital ; Oslo, Norway.
Bjarne
B
Bogen
ACT, Adoptive cell therapy; APC, Antigen-presenting cell; Ag, Antigen; CD4+ T cell response; IFN, Interferon gamma; Id, idiotype; LPS, Lipopolysaccharide; NK, Natural killer; SCID, Severe combined immunodeficiency; TAM, Tumor-associated macrophage; TCR-Tg, T-cell receptor transgenic; bystander killing; macrophage cytotoxicity; multiple myeloma