Immune Cell Types and Secreted Factors Contributing to Inflammation-to-Cancer Transition and Immune Therapy Response

Summary: Although chronic inflammation increases many cancers’ risk, how inflammation facilitates cancer development is still not well studied. Recognizing whether and when inflamed tissues transition to cancerous tissues is of utmost importance. To unbiasedly infer molecular events, immune cell types, and secreted factors contributing to the inflammation-to-cancer (I2C) transition, we develop a computational package called “SwitchDetector” based on liver, gastric, and colon cancer I2C data. Using it, we identify angiogenesis associated with a common critical transition stage for multiple I2C events. Furthermore, we infer infiltrated immune cell type composition and their secreted or suppressed extracellular proteins to predict expression of important transition stage genes. This identifies extracellular proteins that may serve as early-detection biomarkers for pre-cancer and early-cancer stages. They alone or together with I2C hallmark angiogenesis genes are significantly related to cancer prognosis and can predict immune therapy response. The SwitchDetector and I2C database are publicly available at www.inflammation2cancer.org. : Chen et al. develop the SwitchDetector package for transcriptome module detection during inflammation-to-cancer (I2C) stage transitions. They show that angiogenesis is a common critical event for I2C in multiple cancers. The data also suggest that immune cells and secreted cytokines contribute to the I2C transition. Keywords: inflammation, cancer, network analysis, microenvironment, secreted factor, biomarker, cancer transition, immune therapy, cancer surviva