Two receptor theory in innate activation: studies on the receptors for bacillus Culmet guillen-cell wall skeleton (BCG-CWS)
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Activation of the innate immune system is a prerequisite for the maturation of dendritic cells (DC) and macrophages (M?) followed by clonal expansion of the lymphocytes, targeting cells expressing 'non-self' angitens. Microbes usually have a component competent to active DC/M? for antigens presentation. This component has been colled adjuvant, but recently renamed pathogen-associated molecular pattern (PAMP) or modulin based on its molecular identification. Here, we propose the hypothesis that DC/M? express two sorts of receptors for PAMP, whose signaling pathways lead to a sufficient antigen (Ag)-presenting state. In bacterial infection, a Toll-like receptor (TLR) and an uptake receptor participate in DC maturation and M? activation. Likewise, with a number of viruses, two of the receptors with short consensus repeats (SCR), immunoglobulin-like domains or chemokine receptor-like motifs etc. induce functional modulation of DC/M?. In immune therapy for cancer, primary activation of the innate system would be essential for tumor Ag-specific T cell augmentation. Cancer cells express tumor-associated Ag but barely co-express PAMP, which situation does not allow for the activation of innate immune responses. Supplementing tumor-associated Ag with PAMP may be an effective therapy for patients with cancer. Here, we discuss the possibility of an innate immune therapy for cancer with references to bacillus Culmet guillen cell-wall skeleton (GCG-CWS).
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T. Seya, Department of Immunology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka 537, Japan