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MIF Is Necessary for Late-Stage Melanoma Patient MDSC Immune Suppression and Differentiation.


ABSTRACT: 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 E(2) (PGE(2)). 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.

SUBMITTER: Yaddanapudi K 

PROVIDER: S-EPMC4740231 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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MIF Is Necessary for Late-Stage Melanoma Patient MDSC Immune Suppression and Differentiation.

Yaddanapudi Kavitha K   Rendon Beatriz E BE   Lamont Gwyneth G   Kim Eun Jung EJ   Al Rayyan Numan N   Richie Jamaal J   Albeituni Sabrin S   Waigel Sabine S   Wise Ashley A   Mitchell Robert A RA  

Cancer immunology research 20151124 2


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 sough  ...[more]

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