Erythropoietin increases macrophage-mediated T cell suppression.
Erythropoietin (EPO), used to treat anemia in cancer patients, has been reported to accelerate tumor progression and increase mortality. Research of the mechanism for this effect has focused upon EPOR expression by tumor cells. We model the high macrophage to lymphocyte ratio found in tumor microenvironments (TMEs) by culturing peritoneal cavity (PerC) cells that naturally have a high macrophage to T cell ratio. Following TCR ligation, C57BL/6J PerC T cell proliferation is suppressed due to IFNγ-triggered inducible nitric oxide synthase (iNOS) expression. EPO was tested in the PerC culture model and found to increase T cell suppression. This effect could be abrogated by inhibiting iNOS by enzyme inhibition, genetic ablation, or blocking IFNγ signaling. Flow cytometry revealed the EPOR on CD11b(+)F4/80(+) macrophages. These results suggest that EPO could increase T cell suppression in the TME by acting directly on macrophages.
Department of Biology, Rider University, Lawrenceville, NJ 08648, USA.
Michelle A
MA
Wood
Department of Biology, Rider University, Lawrenceville, NJ 08648, USA.
Naomi
N
Goldman
Department of Biology, Rider University, Lawrenceville, NJ 08648, USA.
Kelley
K
DePierri
Department of Biology, Rider University, Lawrenceville, NJ 08648, USA.
John
J
Somerville
Department of Biology, Rider University, Lawrenceville, NJ 08648, USA. Electronic address: riggs@rider.edu.
James E
JE
Riggs
D000818:Animals; D039481:CD11b Antigen; D049109:Cell Proliferation; D002478:Cells, Cultured; D004921:Erythropoietin / Q000378:metabolism*; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010529:Peritoneal Cavity / Q000473:pathology*; D017467:Receptors, Erythropoietin / Q000378:metabolism*; D017471:Receptors, Interferon / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D059016:Tumor Microenvironment; D000096743:Interferon gamma Receptor
D039481:CD11b Antigen; D004921:Erythropoietin; D052247:Nitric Oxide Synthase Type II; D017467:Receptors, Erythropoietin; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C496317:Nos2 protein, mouse
EPO; EPOR; Macrophage; Tumor microenvironment; iNOS