Focus research 2022 ImPact team

Pancreatic tumors are notorious for their resistance to immunotherapies. In this context, the ImPACT team has been investigating the therapeutic potential of Toll-like receptor (TLR) agonist molecules, which are expressed in tumors, and have shown anti-tumor activity in other contexts. In vitro, treatment with TLR7 agonists, and to a lesser extent with TLR2 agonists, inhibits growth and induces apoptosis in pancreatic cancer cells. This effect was observed in vivo, when tumor cells were implanted in the pancreas of immunocompromised mice. In contrast, administration of TLR7 agonists accelerates tumor progression in immunocompetent models of pancreatic cancer. This unexpected effect is due to a repolarization of the tumor microenvironment, and specifically to the presence of macrophages that support tumoral growth. These findings draw attention to the duality of action of TLR7 agonists in pancreatic cancer (PMID:35038581).
Inhibiting difficult-to-target proteins, such as those functioning through protein-protein interactions, with small molecules is a challenge owing to the lack of a well-defined catalytic pocket on these proteins. The team has established a protocol that is a generic method for discovering small molecules inhibiting the interaction between an intracellular antibody and its target. This protocol can be applied to any target or intracellular antibody. (PMID: 35340285).

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