In tumor cells, thyroid hormone analogues non-immunologically regulate PD-L1 and PD-1 accumulation that is anti-apoptotic

Hung Yun Lin, Yu Tang Chin, Ya Jung Shih, Yi Ru Chen, Matthew Leinung, Kelly A. Keating, Shaker A. Mousa, Paul J. Davis

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)34033-34037
Number of pages5
JournalOncotarget
Volume9
Issue number75
DOIs
Publication statusPublished - Sep 1 2018

Keywords

  • Cancer
  • L-thyroxine
  • PD-1/PD-L1 immune checkpoint
  • Tetrac

ASJC Scopus subject areas

  • Oncology

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    Lin, H. Y., Chin, Y. T., Shih, Y. J., Chen, Y. R., Leinung, M., Keating, K. A., Mousa, S. A., & Davis, P. J. (2018). In tumor cells, thyroid hormone analogues non-immunologically regulate PD-L1 and PD-1 accumulation that is anti-apoptotic. Oncotarget, 9(75), 34033-34037. https://doi.org/10.18632/oncotarget.26143