Figure 1. Nkg2d ligands contribute to the synergy of radiotherapy and anti-CTLA-4 mAbs. In mice with poorly immunogenic murine carcinoma cells treated with an anti-CTLA-4 (CD152) antibody, infiltrating cytolytic T cells did not form stable interactions with tumor cells (I). Radiotherapy promoted stable interactions and tumor cell elimination by inducing retinoic acid early inducible-1 (Rae-1) on tumor cells (II). The interaction of Rae-1 on tumor cells with Nkg2d (killer cell lectin-like receptor subfamily K member 1; Klrk1; Cd314) on infiltrating T cells was required for antitumor activity in mice treated with the anti-CTLA-4 antibody.