Protein flags Car-T cells for digestion by NK cells

The protein B7H6, which is highly expressed on activated human T cells, can flag the cells for clearance by natural killer (NK) cells, weakening the response to CAR-T cell therapies. Oncologist Michael Kilian and colleagues at German cancer research centre in Heidelberg demonstrated that these flagged T cells can be abundant among T cell populations in tumour tissue and among therapeutic, CD19-targeting CAR-T cells, indicating that NK clearance might be responsible in part for diminishing antitumor responses.

When the researchers genetically knocked out B7H6, CAR T cell expansion and persistence increased. Thus, Kilian et al. suggest it could be a new immune checkpoint molecule to target in therapies for cancer and immune diseases.

The researchers identified B7H6 during screening of NK cell ligands on human T cells. In humanised mouse models of leukemia, B7H6 flagging limited the persistence and antitumour activity of therapeutically delivered CAR-T cells. Natural killer cells were also more abundant than T cells in a group of patients with relapsed esophageal squamous cell carcinoma who had failed to respond to checkpoint inhibitor treatment, the researchers found.