IFNG and neoplasm: Multiple tumor-intrinsic molecular mechanisms have been identified for primary resistance to immunotherapy: lack of T-cell response due to loss of antigen presentation (deletion in beta-2-microglobulin (β2M)), genetic T-cell exclusion (MAPK or PI3K oncogenic signaling, stabilized b-catenin, oncogenic PD-L1 expression), or insensitivity to T cells (mutations in interferon-gamma pathway signaling) [21].