In addition to inducing an effector-dominated lymphocytic immune infiltrate in tumors, we observe that BEMPEG and anti-CTLA-4 increased the activation of tumor infiltrating immune cells, as measured by the increased expression of genes associated with cytotoxic T lymphocyte activation (Icos, Granzyme B, and Ifnγ) (Figure 3) and increased production of several immune stimulatory cytokines in the primary tumor microenvironment (Figure 4) following combined RT, BEMPEG, and anti-CTLA-4, as compared to RT alone. The gene discussed is ICOS; the disease is neoplasm.