CD274 and melanoma: For example, in melanoma cells and colon cancer cells, loss‐of‐function mutations of Janus Kinase 1/2 (JAK1/2) led to a decreased level of PD‐L1, which resulted in the cells becoming resistant to PD1 blockade therapy.[8] On the other hand, oncogenic pathways (such as phosphoinositide 3‐kinases (PI3K) and signal transducer and activator of transcription 3 (STAT3)), have been shown to upregulate the expression of PD‐L1 on tumor cells.