The Rapid Evolution of Chronic Inflammation to Tolerance / Immune Suppression: Mapping Bidirectional Checkpoints

Currently, there is truly a universal lack of knowledge as to exactly how chronic inflammation leads to the initiation of cancer. Likewise, there exists an equal deficiency in knowledge to define the phenomenon of immune “ tolerance”. Tolerance is, however, generally described as the diminished biological response to repeated or sustained antigen exposure associated with limitation to efficacy of toll-like receptor (TLR) synthetic lipid A lipoglycans, or microbial antigen molecular pattern (MAMP) based tumor immune therapies. The current work was designed to gain greater understanding into these questions, by employing a model of sustained antigenic TLR4 activation with gram-negative cell wall (LPS) for up to 11 days in macrophages under highly controlled conditions.