Helminth parasites and cancer-causing tumors condition human monocytes similarly: insights into parallel mechanisms of immune evasion

Abstract

Abstract A number of features of the host-parasite interface are reminiscent of those that are also observed at the host-cancer interface. Both cancer cells and parasites establish a tissue microenvironment that leads to immune evasion and may be related to alterations in function of various innate cells. Here, we investigate how the phenotype and function of human monocytes is altered by exposure to tumors and if these functional and phenotypic alterations parallel those induced by exposure to helminth parasites. Thus, human monocytes were exposed to three different cancer cell lines (breast, ovarian, or glioblastoma) or to live microfilariae (mf) of Brugia malayi – a causative agent of lymphatic filariasis. After 2 days of culture, cells were harvested, sorted and assessed for mRNA expression, phenotype and function. Monocytes exposed to tumor cell lines showed markedly upregulated expression of M1-associated (TNF-a, IL-1b, IL-8), M2-associated (CCL13, CD206) and Mreg-associated (IL-10, IDO, TGF-b) genes. Similar to cancer cells, but less dramatically mf altered the mRNA expression of IL-1b, CCL13 and IL-8. Similar to the exposure to cancer cell lines, exposure of monocytes to live mf significantly (p<0.05) induced the cell surface expression of the inhibitory ligands PDL1 and PDL2. Finally, exposure of monocytes to cancer cell lines increased the phagocytic ability of these cells, but reduced their ability to induce T cell proliferation, an effect shown to be reversible by PDL1/PD1 blockade. Our data suggest that despite the fact that helminth parasites and tumor cell lines are extraordinarily disparate, they share the ability to alter the phenotype and function of human monocytes and may also share a common mechanism of immune evasion.