IFNG and neoplasm: This highlights that the presence or absence of LOF variants in the IFN-γ pathway in a tumor biopsy is not an absolute determinant of ICB response64; rather, the outcome depends on multiple factors, including the penetrance of the mutation itself (i.e., zygosity), tumor clonal architecture, co-occurring mutations, tumor mutational burden, oncogenic signaling, tumor microenvironment, antigen presentation, and immune checkpoint engagement.4