Recent investigations of the primary tumor microenvironment in colorectal cancer allowed the uncovering of four major intra-tumor immune profiles respectively characterized by: 1) a strong and coordinated cytotoxic Th1 immune phenotype expressing CD8+, CD45RO+ T cells, the transcription factor T-box protein 21 (T-bet), interferon regulatory factor (IRF)-1, interferon (IFN)-γ, granulysin and granzyme-B; 2) tumor angiogenesis (VEGF); 3) non-coordinated immune responses and, 4) a weak immune reactive phenotype [14,45]. The gene discussed is TBX21; the disease is neoplasm.