The immune microenvironment is highly heterogeneous and unique to each tumor type, and different mechanisms of resistance to ICI therapy, including tumor cell-intrinsic (PD-L1 expression, mutational burden, neoantigen expression, epigenetic variations, interferon-γ signaling, and antigen presentation pathways) and tumor cell-extrinsic (microbiome, PD-L1 expression on immune cells, tumoral and peripheral immune cell composition) mechanisms, have been explored.23,31. This evidence concerns the gene CD274 and neoplasm.