An important novelty is that the absence of the Ligand-1 is related to a dysfunction of the beta-catenin/wnt molecular pathway, which is responsible for a cold microenvironment and a low efficacy of ICIs [19], suggesting that a PD-L1 negative stain could be surrounded by a cold tumor microenvironment (lack of infiltrating lymphocytes), which is represented in our model by the TIME-s sample. The gene discussed is CTNNB1; the disease is neoplasm.