CD4 and breast cancer: Markedly increased frequencies of CD4+ and CD8+ T cells expressing markers of activation (PD-1, 4-1BB), differentiation (CX3CR1), and effector phenotype (KLRG1) was observed in ISIM-treated mice compared to untreated mice (Fig. 2b), suggesting effective activation of adaptive T cell immunity in mice bearing orthotopic mammary tumors with brain metastatic disease in response to ISIM.