Determining antitumor responses to variable cadherin expression

Abstract Cancer immunotherapy has dramatically transformed the treatment of many cancers. Despite this, several limitations exist. For example, in some patients’ cancer can become resistant to immunotherapy and relapse is common. Therefore, it is essential to identify new targets for intervention. Our laboratory previously showed that KLRG1, which has two main ligands E-cadherin and N-cadherin, is a potential target. However, cadherin has many roles including a role in epithelial mesenchymal transition. To examine the KLRG1-cadherin axis in antitumor responses we used CRISPR/Cas9 and retroviral overexpression methods to develop a library of B16–F10 melanoma and 4T1 breast cancer cell lines with variable cadherin expression. The appropriate expression of E- and N-cadherin on the cells in this library was confirmed by both flow cytometry and Western blot. We then demonstrated that the modulation of cadherins does not alter cell proliferation rates in vitro. Importantly, in both models, we find that E-cadherin expressing cell lines cause significantly more mortality than E-cadherin deficient parental cell lines. Together, these findings suggest that the KLRG1-cadherin axis play an important role in antitumor responses. This work was supported by the NIH research Grant R01 AI46709 (L.B.)