抗原ペプチドを用いたメラノーマ免疫治療法とその効果を妨げる免疫反応: B16メラノーマ移植マウスから得られる知見より

抄録

Dendritic cells (DCs) play as a powerful initiator in the development of cytotoxic T-lymphocytes (CTLs) and are capable of invigorating natural killer (NK) cells via their-producing interleukin (IL)-12. Therefore, immunization with melanomaassociated antigen (MAA) peptides in combination with DCs is a widely expected strategy for the treatment of patients with melanoma. In naive mice, administration of MAA peptide-pulsed DCs or application of MAA peptides on corneum barrierdisrupted skin, in which Langerhans cells (LCs) have been maximally activated, effectively develop CTL- and NK cell-mediated anti-melanoma immunity in vivo and the treated mice acquire resistance against transplantation of melanoma cells. However, contrary to this expectation, a considerable number of reports has shown no or weak efficacy of treatment with MAA-pulsed DCs applied to melanoma-bearers, suggesting ineffective generation of cytotoxic cells in a melanoma-bearing state. Our current study has demonstrated that melanoma-infiltrating TGF-β-secreting regulatory T cells take a leading part in this downregulation of antimelanoma immunity. This raises a possibility that elimination of this type of Suppressor cells from melanoma bearers is a successful strategy in DC-MAA-based melanoma immunotherapy. [Skin Cancer (Japan) 2000; 15: 131-137]