What is PD-L1?
Cancer cells express PD-L1 (programmed cell death ligand-1) on their surface, which is a receptor for the PD-1 receptor expressed on the surface of activated T cells, and suppress T cell activity through PD-1/PD-L1 binding, thereby evading immune surveillance1 ), 2) . In recent years, these immune surveillance mechanisms have been applied to cancer treatment, and anti-PD-1 and anti-PD-L1 antibodies have been developed to enhance T cell activation by inhibiting this binding, and their clinical efficacy and safety have been confirmed in various solid cancers3 ), 4) .
However, although resistance to treatment after the initial effect has been observed in many cases, the mechanism of resistance to anti-PD-L1 antibodies remains largely unknown.
Recently, two unique secreted PD-L1 splicing variants lacking the transmembrane domain have been identified in patients with anti-PD-L1-resistant NSCLC5 ) .
It has been suggested that the secreted PD-L1 splicing variant induces resistance to PD-L1 inhibitors by acting as a decoy, and the levels of soluble PD-L1 in plasma (exosome-free) or pleural fluid in patients with the secreted PD-L1 splicing variant were higher than those in healthy donors or patients without the secreted PD-L1 variant.5 ) Furthermore, it has been suggested that the blood concentration of soluble
PD-L1 may predict the clinicopathological characteristics, treatment response, and survival outcomes of cancer patients.6 )