Unveiling the Link Between Inflammation and Adaptive Immunity in Breast Cancer

Inflammation has been recognized as an important driver in the development and growth of malignancies. Inflammatory signaling in cancer emerges from the combinatorial interaction of several deregulated pathways. Pathway deregulation is often driven by changes in the underlying gene regulatory networks. Confronted with such complex scenario, it can be argued that a closer analysis of the structure of such regulatory networks will shed some light on how gene deregulation led to sustained inflammation in cancer. Here, we inferred an inflammation-associated gene regulatory network from 641 breast cancer and 78 healthy samples. A modular structure analysis of the regulatory network was carried out, revealing a hierarchical modular structure. Modules show significant overrepresentation score p-values for biological processes unveiling a definite association between inflammatory processes and adaptive immunity. Other modules are enriched for T-cell activation, differentiation of CD8⁺ lymphocytes and immune cell migration, thus reinforcing the aforementioned association. These analyses suggest that in breast cancer tumors, the balance between antitumor response and immune tolerance involving CD8⁺ T cells is tipped in favor of the tumor. One possible mechanism is the induction of tolerance and anergization of these cells by persistent antigen exposure.