To our knowledge, this study is the first to evaluate B 7- H3 expression in NSCLCs treated with anti-PD- 1 therapy and the therapeutic potential of a combination of anti-PD- 1 therapy and B 7- H3 targeting. B 7- H3, an immune-checkpoint molecule, is expressed in various malignancies. Purpose: Anti-programmed-death- 1 (PD- 1) immunotherapy improves survival in non-small cell lung cancer (NSCLC), but some cases are refractory to treatment, thereby requiring alternative strategies. Yonesaka, Kimio Haratani, Koji Takamura, Shiki Sakai, Hitomi Kato, Ryoji Takegawa, Naoki Takahama, Takayuki Tanaka, Kaoru Hayashi, Hidetoshi Takeda, Masayuki Kato, Sigeki Maenishi, Osamu Sakai, Kazuko Chiba, Yasutaka Okabe, Takafumi Kudo, Keita Hasegawa, Yoshikazu Kaneda, Hiroyasu Yamato, Michiko Hirotani, Kenji Miyazawa, Masaaki Nishio, Kazuto Nakagawa, Kazuhiko Blockade of B 7- H 1 represents one approach for cancer immunotherapy.ī 7- H3 Negatively Modulates CTL-Mediated Cancer Immunity. Therefore, upregulation of B 7- H 1 on MDCs in the tumor microenvironment downregulates T-cell immunity. T cells conditioned with the B 7- H 1-blocked MDCs had a more potent ability to inhibit autologous human ovarian carcinoma growth in non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice. Blockade of B 7- H 1 enhanced MDC-mediated T-cell activation and was accompanied by downregulation of T-cell interleukin (IL)-10 and upregulation of IL-2 and interferon (IFN)-gamma. Consistent with this finding, virtually all MDCs isolated from the tissues or draining lymph nodes of ovarian carcinomas express B 7- H 1. B 7- H 1 could be further upregulated by tumor environmental factors. Here, we show that a fraction of blood monocyte-derived myeloid dendritic cells (MDCs) express B 7- H 1, a member of the B 7 family, on the cell surface. Molecular mechanisms of this suppression remain elusive, however. Suppression of dendritic cell function in cancer patients is thought to contribute to the inhibition of immune responses and disease progression. Blockade of B 7- H 1 improves myeloid dendritic cell-mediated antitumor immunity.Ĭuriel, Tyler J Wei, Shuang Dong, Haidong Alvarez, Xavier Cheng, Pui Mottram, Peter Krzysiek, Roman Knutson, Keith L Daniel, Ben Zimmermann, Maria Carla David, Odile Burow, Matthew Gordon, Alan Dhurandhar, Nina Myers, Leann Berggren, Ruth Hemminki, Akseli Alvarez, Ronald D Emilie, Dominique Curiel, David T Chen, Lieping Zou, Weiping
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