COPZ1 depletion in thyroid tumor cells triggers type I IFN response and immunogenic cell death.. COPZ1 depletion in thyroid tumor cells triggers type I IFN response and immunogenic cell death.

Thyroid carcinoma (TC) is generally associated with good prognosis, nevertheless no effective treatments are available for aggressive forms not cured by current therapies. We previously identified the coatomer protein complex zeta 1 (COPZ1) as a new putative therapeutic target for TC, since its depletion impairs the viability of tumor cells, leads to abortive autophagy, ER stress, unfolded protein response and apoptosis, and reduces the tumor growth of TC xenograft models. By combining genomic, proteomic and functional approaches, we now provide evidence that COPZ1 silencing stimulates a type I IFN-mediated viral mimicry response, boosts the production of several inflammatory molecules and induces immunogenic cell death, which in turn promotes dendritic cell maturation and T cell activation. Collectively, our findings indicate that COPZ1 targeting could be exploited as a new strategy to kill cancer cells while stimulating anti-tumor T cell responses. Overall design: Total RNA samples from Nthy-ori 3–1 (SV-40 immortalized normal human thyroid follicular cells) and TPC-1 (papillary thyroid carcinoma) cell lines that were transfected with siRNA oligos directed to COPZ1 gene (siCOPZ1) or siRNA Universal Negative Control (non-targeting: siNT). All experiments were performed in triplicate wells for each condition.