CELL INTELLIGENCE · 肿瘤细胞治疗研究

The most significant advantage of immune checkpoint inhibitors for patients with melanoma is their durable benefits. Particularly, most patients who achieve a complete response maintain a long-term relapse-free survival, even after the cessation of treatment. However, at present, more than half of patients cannot achieve such durable response. Therefore, it is necessary to elucidate mechanisms to achieve durable responses. The objectives of this study are to identify and characterize the molecules that mediate the durable antimelanoma T-cell response. We identified CD276 as a molecule that was downregulated in the regressing lesions of the durable responders. In vitro analysis revealed that exposure to IFN-γ released from activated T cells decreased CD276 expression in melanoma cells. In the autologous coculture assay, the abrogation of CD276 on melanoma cells significantly enhanced recognition and lysis by tumor-infiltrating lymphocytes. An immunohistochemistry analysis showed a tendency toward better progression-free survival after anti-PD-1 therapy in the group with low CD276 expression. We demonstrated that the inhibition of both PD-L1 and CD276 enhanced the antimelanoma response of in vitro tumor-infiltrating lymphocytes. In conclusion, inhibition of CD276 signaling has the potential to enhance the long-term therapeutic efficacy of immune checkpoint inhibitors.