Colorectal cancer (CRC) is the second major cause of cancer-related deaths. Notably, immune checkpoint blockade therapy has become a promising treatment for many cancer patients. However, the majority of CRC patients do not respond to this therapy due to poor T-cell infiltration and downregulated immune checkpoint genes. Elucidating tumor-cell intrinsic mechanisms that inhibit antitumor T-cell responses and developing strategies to boost T cell infiltration is critical to improving immune checkpoint blockade therapy in CRC patients. Tumors use a variety of mechanisms to evade, deceive and suppress the host immune system. This presentation will cover, the role of tumor secreted exosomes and the gut microbiome in the regulation of tumor immune response and metabolic interactions. The novel discoveries in this area of investigation will provide insights in stimulating tumor-specific T cell response and form the foundation for a novel anticancer therapeutic strategy.