TLR7 agonists have dual effect on pancreatic tumors that jeopardize their use in clinics

Toll like receptors (TLR) are key players in the innate immune system, but their role in pancreatic cancer, a disease with no cure that largely escapes immune control, can be dual. Thus, we aimed to clarify the therapeutic potential of TLR ligands, mainly TLR7 ligands, in experimental models. In vitro, TLR7 ligands strongly inhibit cancer cell proliferation, alter cancer cells cell cycle and induce cell death by apoptosis. In vivo, TLR7 agonist significantly delay the growth of tumors engrafted in immunocompromised mice. However, TLR7 ligands instead increase tumor growth and accelerates animal death when tumors are engrafted in immunocompetent models. Further investigations reveal that TLR7 agonists modulate the intratumoral content and phenotype of macrophages, that account for TLR7 promotion of tumor growth. Collectively, our findings shine a light on the duality of action of TLR7 agonists in experimental cancer models and calls into question their use for pancreatic cancer therapy.

TLR7 agonists may have potential to inhibit pancreatic cancer cell proliferation, but its action on tumor macrophages calls into question their use for pancreatic cancer therapy

Macrophage infiltration in experimental pancreatic tumors treated with TLR7 agonists / Infiltration de macrophages dans des tumeurs pancréatiques expérimentales traitées par des agonistes TLR7

Collaborations and acknowledgements