👉Inhibition of BRAF signaling in BRAF-mutated papillary thyroid cancer may be able to induce PD-L1 expression through the activation of the mTOR pathway in vitro.
👉Atish Mohanty, PhD, of the City of Hope National Medical Center in Duarte, California, presented there work at the 2020 Multidisciplinary Head and Neck Cancers Symposium in Scottsdale, Arizona (Abstract 336).
👉A total of 19 high- and low-risk papillary thyroid cancer cases from 2013 to 2018 with available paraffin-embedded archived tissue were identified for this study.
👉Initial characterization of BRAF mutation status was completed via RNA analysis using NanoString, which identified 13 tumors with BRAF V600–activating mutations, one BRAF V600R–activating mutation, and 5 BRAF wild-type tumors.
👉Researchers used one BRAF wild-type and two BRAF-mutant papillary thyroid cell lines for proof of concept.
👉The BRAF inhibitors dabrafenib and vemurafenib were added to the cell lines in vitro, as was the Rho-associated protein kinase inhibitor Y27632 (to inhibit mTOR).
👉Additionally, BRAF-specific small interfering RNAs (siRNA) were transfected into the papillary thyroid cell lines.
👉Researchers found there was a higher expression of PD-L1 and CTLA-4 in papillary thyroid cancer cell samples that had mutant BRAF genes.
👉This association was confirmed in the two papillary thyroid cancer cell lines with mutated BRAF.
👉Addition of dabrafenib or vemurafenib in the BRAF-mutated cell lines was reported to induce PD-L1 expression without affecting cell viability.
👉In addition, knockdown of BRAF via siRNA in these same cell lines confirmed PD-L1 upregulation in vitro.
👉A potential mechanism for the upregulation of PD-L1 is through AKT-mTOR signaling, as mTOR inhibition was found to cause a strong reduction in the expression of PD-L1 in the BRAF-mutated cell lines.
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