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Cancer Res. 2009 Jul 15;69(14):5901-7. doi: 10.1158/0008-5472.CAN-08-4816. Epub 2009 Jun 30.

Secretion of tumor-specific antigen by myeloma cells is required for cancer immunosurveillance by CD4+ T cells.

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Center for Immune Regulation, Institute of Immunology, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway.


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.

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