Nonetheless, whether the therapeutic effects of ICI treatment in HER2-positive CRC correlate with the programmed death-ligand 1 (PD-L1) protein expression and the status of the tumor microenvironment (TME) immune cells, including T cells, macrophages, natural killer (NK) cells, B cells, and tertiary lymphoid structures (TLSs), are unknown. This evidence concerns the gene CD274 and neoplasm.