Mechanisms specifically involved in immune checkpoint blockade resistance include insufficient tumor antigenicity, tumor-intrinsic interferon-γ signaling, tumor-intrinsic loss of MHC, tumor dedifferentiation and stemness, and regulation by oncogenic signaling, with a particular focus on certain pathways (the WNT–β-catenin pathway, the mitogen-activated protein kinase (MAPK) pathway, the cyclin-dependent kinase 4 (CDK4)–CDK6 pathway) and the pathways induced by loss of PTEN [25]. Here, CDK4 is linked to neoplasm.