We uncovered tumor-intrinsic differences that may underlie the differential responses to ICI by establishing and employing two KPPA SCC tumor lines, TAb2 vs. TCh3, both of which harbor TP53 deletion and PIK3CA hyperactivation and originated from the same K15.CrePR1(+)p53f/fPIK3CAc/c mouse. Here, TP53 is linked to neoplasm.