Barring aberrant vasculature, the significant hurdles for immune response cascade for combinatorial ImT are as follows: a) immediate counter-reactive homeostasis response for ICD mitigates the immunological reaction (e.g., the recruitment of MDSCs inhibiting the activity of CD8+ T cells and DCs instantly after SBRT); b) generation of massive amounts of nonspecific antigens drowning the cancer cell-specific antigens; and c) the immunosuppressive nature of therapies, especially local RT, when given over a long time (immune exhaustion). This evidence concerns the gene CD8A and cancer.