Repositioning liothyronine for cancer immunotherapy by blocking the interaction of immune checkpoint TIGIT/PVR.
Level 5 - mechanism / opinion, no new human data
Preclinical bench, in vitro, and animal research with no human clinical trial data.
PubMed 32894141 · doi:10.1186/s12964-020-00638-2
What was done
The authors evaluated PVR expression using cancer databases (TCGA, Oncomine, GEO) and flow cytometry in cancer cell lines. They performed virtual docking screening of natural product compounds against PVR. Candidate binding was assessed via biolayer interferometry, microscale thermophoresis, and cell-based blocking assays. In vitro effects were evaluated using MTT assays, peripheral blood mononuclear cell (PBMC) activation assays, and Jurkat-hTIGIT/CHOK1-hPVR coculture assays. In vivo antitumor efficacy and mechanism were evaluated in MC38 tumor-bearing mice and immune cell depletion models.
What was found
Liothyronine was identified as a ligand that binds PVR and blocks the TIGIT/PVR interaction. In vitro, it enhanced CD4+ and CD8+ T-cell function in PBMCs and restored IL-2 secretion in TIGIT/PVR coculture systems, without directly affecting tumor cell proliferation. In vivo, liothyronine inhibited MC38 tumor growth, enhanced CD8+ T-cell infiltration, and required CD4+ T cells, CD8+ T cells, and NK cells for its antitumor efficacy. The abstract reports no numerical values, effect sizes, or statistical metrics.
Why it matters
TIGIT/PVR is an emerging immune checkpoint target primarily targeted with monoclonal antibodies. This study identifies liothyronine, an existing drug, as a potential small-molecule inhibitor for repurposing in cancer immunotherapy.
Limits
All findings are preclinical, derived from in silico modeling, cell lines, and a single murine tumor model (MC38). The abstract reports no quantitative data (such as binding affinities, tumor volume reductions, or sample sizes). Potential systemic endocrine toxicity from administering a thyroid hormone at immunomodulatory doses was not addressed.
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