テラワキ　セイゴウ   Seigo Terawaki   寺脇　正剛    所属   川崎医科大学  医学部 基礎医学　分子遺伝医学    職種   特任講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	PD-1 blockade inhibits hematogenous spread of poorly immunogenic tumor cells by enhanced recruitment of effector T cells.
掲載誌名	正式名：International immunology 略　 称：Int Immunol ISSNコード：09538178/09538178
掲載区分	国外
巻・号・頁	17(2),pp.133-144
著者・共著者	Iwai Yoshiko, Terawaki Seigo, Honjo Tasuku
担当区分	2nd著者
発行年月	2005/02
概要	Since metastasis is the major cause of death for cancer patients, there is an urgent need to develop new therapies to control hematogenous dissemination of cancer cells. Previously we and others demonstrated a novel mechanism that allows tumors to escape from the host immune response by expressing PD-L1 which can negatively regulate immune response through the interaction with PD-1, an immunoinhibitory receptor belonging to the CD28 family. In this study, we report that hematogenous spread of poorly immunogenic B16 melanoma cells to the liver was inhibited in PD-1-deficient mice. After inoculation to spleen, PD-L1 was induced on tumor cells, which did not express PD-L1 in vitro. As compared with wild-type mice, intrasplenic injection of B16 cells into PD-1-deficient mice showed enhanced induction of effector T cells in spleen, prolonged T cell proliferation and cytokine production, and augmented homing of effector T cells to tumor sites in the liver, resulting in accumulation of effector T cells in the tumor sites. PD-1 blockade by genetic manipulation or antibody treatment inhibited not only hematogenous dissemination of B16 melanoma cells to the liver on the C57BL/6 background, but also dissemination of CT26 colon cancer cells to the lung on the BALB/c background. These results suggest that PD-1 blockade may be a powerful tool for treatment of hematogenous spread of various tumor cells.
DOI	10.1093/intimm/dxh194
PMID	15611321