Investigating immune suppression mechanisms in cancer may inform on strategies to overcome resistance to current immunotherapies, common across solid tumor types but near ubiquitous in pancreatic ductal adenocarcinoma (PDAC). A recent study by Kemp and colleagues in Cancer Research identified an immuno-modulatory axis originating in tumor-associated macrophages whereby macrophage-derived apolipoprotein E (APOE) activates NF-κB in tumor cells in a paracrine manner, inducing expression of immunosuppressive chemokines. In contrast, APOE promotes antitumor immunity in other cancer types including melanoma, highlighting the context dependency of APOE signaling and its impact on the tumor microenvironment. As new immunotherapy approaches increasingly aim to modulate both the myeloid and lymphoid compartments of the PDAC immune milieu, identification of specific mechanisms that foster macrophage-mediated immune suppression may facilitate the development of effective strategies that enable the immune system to tackle these tumors.See related article by Kemp et al., p. 4305.
©2021 American Association for Cancer Research.