Unique Ectopic Lymph Node-Like Structures Present in Human Primary Colorectal Carcinoma Are Identified by Immune Gene Array Profiling

We hypothesized that immune gene-related signatures would predict the presence of unique histological features of lymphoid cell infiltrates in colorectal carcinoma (CRC) that correlate with clinical parameters. Metagene analysis with gene chip technology was performed on 326 CRCs, which were then sorted by low versus high gene scores. Microscopically, CRCs with a high gene score revealed a marked host immune response organized, remarkably, as lymphoid follicles. Proliferation involved both B and T cells. In every case, the presence of CD79a+ B-cell precursors was identified, suggesting that the lymphoid follicles represent newly formed, ectopic lymph node-like structures. CD21+ dendritic cells were present within the follicular germinal centers, and CD3+ T cells were localized mainly in the parafollicular cortex zone surrounding the B-cell area of the follicles. A strong correlation between a 12-chemokine gene subset of the molecular profile and the presence of ectopic lymph node-like structures was associated with better patient survival independent of tumor staging, site location, microsatellite instability or stability, and patient treatment. These findings suggest beneficial, intratumoral immune cell priming and raise the possibility of immunotherapy intervention decisions based on molecular signatures that can identify the presence of tumor-localized, ectopic lymph node-like structures.