TGF-ß builds a dual immune barrier in colorectal cancer by impairing T cell recruitment and instructing immunosuppressive SPP1+ macrophages

Poor prognosis colorectal cancer (CRC) is linked to a TGF-ß-activated tumor microenvironment that suppresses immune responses. Inhibiting TGF-ß signaling promotes T cell infiltration and enhances immune checkpoint blockade effectiveness, highlighting a network of genetic programs that prevent effective immune responses and clonal expansion of T cells, ultimately enabling metastatic growth. Overall design: Tumor microenvironment from liver metastasis from colorectal cancer mouse tumor organoids under three different treatments plus controls. Different samples were analyzed: whole tumor microenvironment, T cells only and fibroblasts only.