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

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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
Publication statusPublished - Sep 1 2018

Fingerprint

Thyroid Hormones
Neoplasms
Lymphocytes
CD4-Positive T-Lymphocytes
Cell Surface Receptors
Thyroxine
Integrins
Macrophages
Cell Membrane
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Oncology

Cite this

Lin, H. Y., Chin, Y. T., Shih, Y. J., Chen, Y. R., Leinung, M., Keating, K. 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.

In tumor cells, thyroid hormone analogues non-immunologically regulate PD-L1 and PD-1 accumulation that is anti-apoptotic. / Lin, Hung Yun; Chin, Yu Tang; Shih, Ya Jung; Chen, Yi Ru; Leinung, Matthew; Keating, Kelly A.; Mousa, Shaker A.; Davis, Paul J.

In: Oncotarget, Vol. 9, No. 75, 01.09.2018, p. 34033-34037.

Research output: Contribution to journalArticle

Lin, HY, Chin, YT, Shih, YJ, Chen, YR, Leinung, M, Keating, KA, Mousa, SA & Davis, PJ 2018, 'In tumor cells, thyroid hormone analogues non-immunologically regulate PD-L1 and PD-1 accumulation that is anti-apoptotic', Oncotarget, vol. 9, no. 75, pp. 34033-34037.
Lin, Hung Yun ; Chin, Yu Tang ; Shih, Ya Jung ; Chen, Yi Ru ; Leinung, Matthew ; Keating, Kelly A. ; Mousa, Shaker A. ; Davis, Paul J. / In tumor cells, thyroid hormone analogues non-immunologically regulate PD-L1 and PD-1 accumulation that is anti-apoptotic. In: Oncotarget. 2018 ; Vol. 9, No. 75. pp. 34033-34037.
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