@article{f7e825d1a5574b19b66237c0c30d9fdb,
title = "In tumor cells, thyroid hormone analogues non-immunologically regulate PD-L1 and PD-1 accumulation that is anti-apoptotic",
abstract = "The PD-1/PD-L1 immune checkpoint involving tumor cells and host immune defense lymphocytes is a well-studied therapeutic target in oncology. That PD-1 and PD-L1 may have additional functions within tumor cells that are independent of the checkpoint is indicated by actions of a thyroid hormone analogue, L-thyroxine (T4), on these checkpoint components. Acting at a cell surface receptor on plasma membrane integrin αvβ3, T4 stimulates intracellular accumulation of PD-L1 in cancer cells. In these thyroid hormone-treated cells, T4-induced PD-L1 is non-immunologically anti-apoptotic, blocking activation of p53. Several laboratories have also described accumulation of PD-1 in a variety of cancer cells, not just immune defense lymphocytes and macrophages. Preliminary observations indicate that T4 stimulates intracellular accumulation of PD-1 in tumor cells, suggesting that, like PD-L1, PD-1 has non-immunologic roles in the setting of cancer. Where such roles are anti-apoptotic, thyroid hormone-directed cancer cell accumulation of PD-1 and PD-L1 may limit effectiveness of immunologic therapy directed at the immune checkpoint.",
keywords = "Cancer, L-thyroxine, PD-1/PD-L1 immune checkpoint, Tetrac",
author = "Lin, {Hung Yun} and Chin, {Yu Tang} and Shih, {Ya Jung} and Chen, {Yi Ru} and Matthew Leinung and Keating, {Kelly A.} and Mousa, {Shaker A.} and Davis, {Paul J.}",
note = "Funding Information: This work was supported in part by the “TMU Research Center of Cancer Translational Medicine” from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Funding Information: Ministry of Education (MOE) in Taiwan and grants from Ministry of Science and Technology, Taiwan (MOST 104-2314-B-038-046 -MY3; MOST105-2320-B-038-006). Publisher Copyright: {\textcopyright} Lin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",
year = "2018",
month = sep,
day = "1",
doi = "10.18632/oncotarget.26143",
language = "English",
volume = "9",
pages = "34033--34037",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals LLC",
number = "75",
}