| Autor: |
Robert A. Mitchell, Ashley Wise, Sabine Waigel, Sabrin Albeituni, Jamaal Richie, Numan Al Rayyan, Eun Jung Kim, Gwyneth Lamont, Beatriz E. Rendon, Kavitha Yaddanapudi |
| Rok vydání: |
2023 |
| DOI: |
10.1158/2326-6066.c.6548812.v1 |
| Popis: |
Highly aggressive cancers “entrain” innate and adaptive immune cells to suppress antitumor lymphocyte responses. Circulating myeloid-derived suppressor cells (MDSC) constitute the bulk of monocytic immunosuppressive activity in late-stage melanoma patients. Previous studies revealed that monocyte-derived macrophage migration inhibitory factor (MIF) is necessary for the immunosuppressive function of tumor-associated macrophages and MDSCs in mouse models of melanoma. In the current study, we sought to determine whether MIF contributes to human melanoma MDSC induction and T-cell immunosuppression using melanoma patient-derived MDSCs and an ex vivo coculture model of human melanoma-induced MDSC. We now report that circulating MDSCs isolated from late-stage melanoma patients are reliant upon MIF for suppression of antigen-independent T-cell activation and that MIF is necessary for maximal reactive oxygen species generation in these cells. Moreover, inhibition of MIF results in a functional reversion from immunosuppressive MDSC to an immunostimulatory dendritic cell (DC)–like phenotype that is at least partly due to reductions in MDSC prostaglandin E2 (PGE2). These findings indicate that monocyte-derived MIF is centrally involved in human monocytic MDSC induction/immunosuppressive function and that therapeutic targeting of MIF may provide a novel means of inducing antitumor DC responses in late-stage melanoma patients. Cancer Immunol Res; 4(2); 101–12. ©2015 AACR. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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