Claudin-6 mediates an embryonic stem cell-driven antitumor response against breast cancer.

Stem cells are emerging sources of antigens for cancer immunotherapy. Here, we used TNG-A mouse embryonic stem cells to trigger an anticancer response against tumors derived from E0771 mouse breast cancer cells, possibly mediated by the mouse immune system. TNG-A cells were cultured in the presence or absence of two specific kinase inhibitors. While the inhibitors preserved TNG-A pluripotency, their removal altered the morphology, transcriptome, and proteome of TNG-A cells, increasing their similarities with E0771 cancer cells. Double pre-exposure by subcutaneous injection of TNG-A cells followed by E0771 implantation drastically decreased E0771-derived tumor size in mice. Serum cytokine quantifications suggested a transient immune reaction associated with tumor regression. Nevertheless, pre-exposure to TNG-A cells impaired for the tight junction protein Claudin 6 failed to decrease tumor size. Our findings demonstrate the anti-tumor effects of embryonic stem cells and anticipate their potential as an allogenic source for cancer immunotherapy.