Title : The regulatory mechanism and therapeutic application of immune checkpoint in alveolar echinococcosis
Abstract:
Alveolar echinococcosis (AE) is a tumor-like disease predominantly located in the liver caused by persistent infection with the cestode Echinococcus multilocularis. Much evidence has demonstrated that E. multilocularis is a successful parasite through its ability to shape an “immunosuppressive” liver microenvironment to maintain its persistent infection. Therefore, how the parasite evades host immunity becomes an interesting question in several aspects of the pathogenesis of E. multilocularis infection. The role of immune checkpoint receptors has come to the forefront in cancer and chronic viral infection, in which these receptors are highly expressed and are being targeted clinically (such as checkpoint blockade) to improve antitumor and antiviral T-cell responses. Here, based on our series of innovative research in recent years, we demonstrated that immune checkpoint receptors (TIGIT, PD-1 and LAG3) expression were signi?cantly upregulated and associated with T-cell or NK-cell dysfunction in advanced AE patients and in E. multilocularis-infected mice and promoted disease progression. Blocking TIGIT may reverse the functional impairment of T and NK cells and represent a possible approach to immunotherapy against AE. In addition, we found that the resistance to anti PD-1 checkpoint interventions observed in chronic E. multilocularis infection is mainly attributed to the accumulation of G-MDSCs around liver lesions, and targeting MDSCs promotes antiparasitic T-cell immunity and enhances the ef?cacy of PD-1 blockade. Our ?ndings provide preclinical evidence in support of targeting MDSC or combining such an approach with checkpoint blockade in patients with advanced AE, a severe disease with only limited treatment options.
