Secretion of tumor-specific antigen by myeloma cells is required for cancer immunosurveillance by CD4+ T cells.
Tumor-specific CD4(+) T cells orchestrate the adaptive immune responses against cancer. We have previously shown that CD4(+) T cells recognize MHC class II-negative myeloma cells indirectly by collaborating with tumor-infiltrating macrophages. We, here, hypothesize that this critical step may be dependent on secretion of tumor-specific antigens by cancer cells. This was investigated using T-cell receptor-transgenic mice, in which CD4(+) T cells mediate rejection of syngeneic MOPC315 myeloma cells. We analyzed the immune response against myeloma cell variants, which either secrete or retain intracellularly a tumor-specific idiotypic (Id) antigen. Our results reveal that CD4(+) T cells helped by macrophages are capable of detecting nonsecreted tumor antigens from MHC class II-negative cancer cells. However, Id secretion was required for successful myeloma immunosurveillance. Antigen secretion resulted in stronger priming of naive myeloma-specific CD4(+) T cells in tumor-draining lymph nodes. Secretion of antigen by at least some cancer cells within a tumor was shown to facilitate immunosurveillance. Treatment by local injection of purified tumor-specific antigen successfully enhanced immunity against nonsecreting myeloma cells. Collectively, the data indicate that antigen concentration within the tumor extracellular matrix must reach a certain threshold to allow successful cancer immunosurveillance by CD4(+) T cells.
Corthay
Alexandre
A
Center for Immune Regulation, Institute of Immunology, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway. Alexandre.Corthay@medisin.uio.no
Lundin
Katrin U
KU
Lorvik
Kristina Berg
KB
Hofgaard
Peter O
PO
Bogen
Bjarne
B
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D039481:CD11b Antigen / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D007157:Immunologic Surveillance / Q000276:immunology*; D016219:Immunotherapy, Adoptive; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008822:Mice, Transgenic; D009101:Multiple Myeloma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D009374:Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D047368:Tumor Burden / Q000276:immunology
D000951:Antigens, Neoplasm; D039481:CD11b Antigen; D011948:Receptors, Antigen, T-Cell