Research Perspectives:

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 and Paul J. Davis _

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Oncotarget. 2018; 9:34033-34037. https://doi.org/10.18632/oncotarget.26143

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Hung-Yun Lin1,2,3,4, Yu-Tang Chin1,2, Ya-Jung Shih1,2, Yi-Ru Chen1,2, Matthew Leinung5, Kelly A. Keating6, Shaker A. Mousa6 and Paul J. Davis5,6

1 PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan

2 Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan

3 Traditional Herbal Medicine Research Center of Taipei Medical University Hospital, Taipei, Taiwan

4 TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan

5 Department of Medicine, Albany Medical College, Albany, NY, USA

6 Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA

Correspondence to:

Paul J. Davis, email: [email protected]

Keywords: L-thyroxine; PD-1/PD-L1 immune checkpoint; cancer; tetrac

Received: August 25, 2018    Accepted: September 08, 2018    Published: September 25, 2018


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.

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