@article{19d9d17812b84ff689ff444b7d96e545,
title = "Adipose PD-L1 Modulates PD-1/PD-L1 Checkpoint Blockade Immunotherapy Efficacy in Breast Cancer",
abstract = "Programmed death-ligand 1 (PD-L1) and its receptor programmed cell death protein 1 (PD-1) modulate antitumor immunity and are major targets of checkpoint blockade immunotherapy. However, clinical trials of anti-PD-L1 and anti-PD-1 antibodies in breast cancer demonstrate only modest efficacy. Furthermore, specific PD-L1 contributions in various tissue and cell compartments to antitumor immunity remain incompletely elucidated. Here we show that PD-L1 expression is markedly elevated in mature adipocytes versus preadipocytes. Adipocyte PD-L1 prevents anti-PD-L1 antibody from activating important antitumor functions of CD8+ T cells in vitro. Adipocyte PD-L1 ablation obliterates, whereas forced preadipocyte PD-L1 expression confers, these inhibitory effects. Pharmacologic inhibition of adipogenesis selectively reduces PD-L1 expression in mouse adipose tissue and enhances the antitumor efficacy of anti-PD-L1 or anti-PD-1 antibodies in syngeneic mammary tumor models. Our findings provide a previously unappreciated approach to bolster anticancer immunotherapy efficacy and suggest a mechanism for the role of adipose tissue in breast cancer progression.",
keywords = "Breast cancer, PD-1, PD-L1, PPARgamma antagonist, adipocyte, combination therapy, immune checkpoint, immunotherapy, inflammation and cancer, new targets",
author = "Bogang Wu and Xiujie Sun and Gupta, {Harshita B.} and Bin Yuan and Jingwei Li and Fei Ge and Chiang, {Huai Chin} and Xiaowen Zhang and Chi Zhang and Deyi Zhang and Jing Yang and Yanfen Hu and Curiel, {Tyler J.} and Rong Li",
note = "Funding Information: This work was supported by the HHS | National Institutes of Health (NIH) [CA206529]; HHS | National Institutes of Health (NIH) [DK115219]; Cancer Prevention and Research Institute of Texas (CPRIT) [RP150055]; HHS | National Institutes of Health (NIH) [CA212674]; HHS | National Institutes of Health (NIH) [CA054174]; Cancer Prevention and Research Institute of Texas (CPRIT) [RP170126]; HHS | National Institutes of Health (NIH) [CA205965]; Cancer Prevention and Research Institute of Texas (CPRIT) [RP170345]; HHS | National Institutes of Health (NIH) [T32CA148724]; U.S. Department of Defense (DOD) [W81XWH-17-1-0007]. Funding Information: This work was supported by the HHS | National Institutes of Health (NIH) [CA206529]; HHS | National Institutes of Health (NIH) [DK115219]; Cancer Prevention and Research Institute of Texas (CPRIT) [RP150055]; HHS | National Institutes of Health (NIH) [CA212674]; HHS | National Institutes of Health (NIH) [CA054174]; Cancer Prevention and Research Institute of Texas (CPRIT) [RP170126]; HHS | National Institutes of Health (NIH) [CA205965]; Cancer Prevention and Research Institute of Texas (CPRIT) [RP170345]; HHS | National Institutes of Health (NIH) [T32CA148724]; U.S. Department of Defense (DOD) [W81XWH-17-1-0007]. We thank Dr. Lieping Chen for the PD-L1 KO mouse strain, Drs. Haihui Pan, Reka Chakravarthy, Suresh Kari, Leilei Qi, Li-Ling Lin, Ms. Jie Liu, Ms. Karla M. Gorena, and Ms. Sabrina Smith for technical assistance. The work was supported by grants to RL from NIH (CA206529 and DK115219), CPRIT (RP150055), and the Tom C. & H. Frost Endowment; to YH from NIH (CA212674), DOD (W81XWH-17-1-0007), and the Cancer Prevention and Research Institute of Texas (CPRIT, RP170126); to TJC from NIH (CA205965) and the Owens and Barker Foundations and the Skinner Endowment; to BY from an CPRIT Postdoctoral Training Grant (RP170345); and to HCC from an NIH Postdoctoral Training Grant (T32CA148724). We also thank generous support from the University of Texas Health San Antonio Cancer Center (CA054174). Funding Information: We thank Dr. Lieping Chen for the PD-L1 KO mouse strain, Drs. Haihui Pan, Reka Chakravarthy, Suresh Kari, Leilei Qi, Li-Ling Lin, Ms. Jie Liu, Ms. Karla M. Gorena, and Ms. Sabrina Smith for technical assistance. The work was supported by grants to RL from NIH (CA206529 and DK115219), CPRIT (RP150055), and the Tom C. & H. Frost Endowment; to YH from NIH (CA212674), DOD (W81XWH-17-1-0007), and the Cancer Prevention and Research Institute of Texas (CPRIT, RP170126); to TJC from NIH (CA205965) and the Owens and Barker Foundations and the Skinner Endowment; to BY from an CPRIT Postdoctoral Training Grant (RP170345); and to HCC from an NIH Postdoctoral Training Grant (T32CA148724). We also thank generous support from the University of Texas Health San Antonio Cancer Center (CA054174). Publisher Copyright: {\textcopyright} 2018, {\textcopyright} 2018 The Author(s). Published with license by Taylor & Francis Group, LLC.",
year = "2018",
month = nov,
day = "2",
doi = "10.1080/2162402X.2018.1500107",
language = "English (US)",
volume = "7",
journal = "OncoImmunology",
issn = "2162-4011",
publisher = "Landes Bioscience",
number = "11",
}