Investigating the role of VSIG4-expressing macrophages in steady state and during peritoneal metastasis formation

Activiteit: Talk or presentation at a conference

Description

Despite recent advances in cancer immunotherapy, cancer patients with peritoneal metastasis (PM) have a poor prognosis and low overall survival. During PM, cancer cells encounter immune cells in the peritoneal cavity, such as large peritoneal macrophages (LPMs). 30% of LPMs expresses the surface receptor VSIG4, a complement receptor and a potential immune checkpoint molecule. In this study, the question is raised whether VSIG4+ LPMs are different from VSIG4- LPMs in the peritoneal cavity in steady state and during PM disease progression. Using Flt3Cre-R26YFP reporter mice, we observed that the majority of VSIG4+ LPMs are of embryonic origin, as expected for tissue-resident macrophages (tr-MFs), while VSIG4- LPMs are actually mostly bone marrow-derived. VSIG4+ LPMs display enhanced phagocytic capacity of PhRodo-labeled particles compared to VSIG4- LPMs in vitro. When stimulated with TLR agonists in vitro, both LPM subsets upregulated Il10 gene expression, suggesting an immunosuppressive phenotype. However, upon in vitro co-culture, preliminary data suggest that VSIG4+ LPMs suppress CD8+ T-cell proliferation to a lesser extent than VSIG4- LPMs. Interestingly, the percentage of VSIG4+ LPMs (within the total LPM population) decreased in the peritoneal cavity of murine models of colorectal cancer (MC38) and ovarian cancer (ID8), suggesting a more prominent contribution of immunosuppressive VSIG4- LPMs. The contribution of VSIG4+ LPMs in early and late phases of PM will be investigated by the use of in house produced anti-VSIG4 nanobody constructs.
Periode18 okt 2022
Evenementstitel4th Research Day in Tumor Immunology and Immunotherapy
EvenementstypeConference
LocatieLeuven, Belgium