CD206 Small Molecule Modulators, Their Use and Methods for Preparation

Pancreatic ductal adenocarcinoma (PDA) accounts for more than 90% of pancreatic cancer cases, and it is one of the most aggressive malignancies with a 5-year survival rate of 6%. The high mortality rate caused by PDA is primarily from the lack of early diagnosis – it is often asymptomatic in early stages – and a poor response to conventional chemotherapy and radiotherapy. One of the major immune cell types present in the PDA microenvironment is a subset of macrophages commonly termed tumor-associated macrophages (TAM). TAMs originate, in part, from circ ulating monocytes upon activation by CCL2, a chemotactic chemokine secreted and then recruited to the tumor microenvironment by cytokines expressed by PDA cells.TAMs consist primarily of polarized M2 macrophages which promote tumor growth by secreting immunosuppressive factors that block effector T-cell activation. TAMs express scavenger receptors such as CD206 which facilitate tumor angiogenesis and migration. CD206 is a member of the large C-type lectin receptor family and not found on other TAM population like undifferentiated M0 or M1-like macrophages. CD206high expression and infiltration with CD206high macrophages has been associated with poor clinical outcomes in pancreatic cancer and other solid organ cancers. Current anti-macrophage therapy generally inhibits activation or the recruitment of macrophages (CCL2/CCR2), which lacks specificity towards M2-like macrophages, agonism of M1 signaling via CD40 ligation, or ...
Source: NIH OTT Licensing Opportunities - Category: Research Authors: Source Type: research