MIF-Dependent Control of Tumor Immunity

Noe, Jordan T.; Mitchell, Robert A.

doi:10.3389/fimmu.2020.609948

Cited by 84 publications

(96 citation statements)

References 197 publications

(207 reference statements)

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“…These findings suggested that serum MIF appeared to be an important biological indicator for reflecting disease severity and an independent predictor to detect those who might best benefit from SLIT. MIF is a unique pleiotropic protein which is mainly expressed on monocytes, macrophages, and lymphocytes, and serves as an important pro-inflammatory mediator and immune regulator that participates in innate and adaptive immune responses (Noe and Mitchell, 2020;Liu et al, 2021). Prior publications reported a pivotal role of MIF in the pathogenesis of type 2-mediated inflammation, especially in allergic and autoimmune diseases (Yoshihisa et al, 2011;de Souza et al, 2015;Bozza et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Circulating MIF Associated With Disease Severity and Clinical Response of Sublingual Immunotherapy in House Dust Mite–Induced Allergic Rhinitis

et al. 2021

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Background: Macrophage migration inhibitory factor (MIF) is described as a pro-inflammatory cytokine involved in many inflammatory and allergic disorders, but the role of MIF in allergic rhinitis (AR) remains poorly clarified. The aim of this study was to investigate the association between circulating MIF levels and house dust mite (HDM)-induced AR, and evaluate MIF as a potential biomarker in reflecting disease severity and predicting the clinical response of sublingual immunotherapy (SLIT) in HDM-induced AR patients.Methods: In this study, we enrolled 160 persistent HDM-induced AR patients (AR group), including 48 mild AR patients (MAR group) and 112 moderate–severe AR patients (MSAR group), and 77 healthy controls (HC group). Circulating levels of MIF were measured by ELISA, and the relationship between MIF concentrations and disease severity was assessed. In the MSAR group, 106 patients were assigned to receive SLIT for 3 years. At the end of the study, patients were categorized into good response group and poor response group, and associations between clinical variables or biomarkers and clinical response were analyzed by the multivariate regression analysis.Results: The concentrations of serum MIF were significantly higher in AR patients than in HCs, especially in those with MSAR. Moreover, circulating MIF levels were positively correlated with TNSS, VAS, serum HDM–specific IgE, total IgE, blood eosinophil count, and blood eosinophil percentage (all p < 0.05). Eighty MSAR patients finally completed SLIT, 45 patients obtained good response, and 35 patients resulted in poor response. The serum levels of MIF were significantly lower in the good-response group than in the poor-response group (p < 0.001). The receiver operating characteristic analysis for MIF showed good accuracy for predicting clinical response of SLIT (area under the curve = 0.877, p < 0.001). The multivariate regression analysis demonstrated that serum MIF was an independent factor for SLIT responsiveness.Conclusion: Serum MIF appeared to be an important biological indicator in reflecting disease severity and an independent predictor for clinical responsiveness of SLIT in HDM-induced AR patients.

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Section: Discussionmentioning

confidence: 99%

Circulating MIF Associated With Disease Severity and Clinical Response of Sublingual Immunotherapy in House Dust Mite–Induced Allergic Rhinitis

et al. 2021

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“…MIF affects both tumor progression and tumor-associated immune responses. It is becoming increasingly evident that MIF plays an important regulatory role in governing TAM-dependent tumor initiation, progression, and metastatic disease phenotypes, although a unifying mechanism that explains how MIF contributes to this seemingly divergent M1 and M2 macrophage phenotypes is still lacking [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Influence of Epstein–Barr virus and human papillomavirus infection on macrophage migration inhibitory factor and macrophage polarization in nasopharyngeal carcinoma

Feng

et al. 2021

BMC Cancer

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Background To assess the effects of Epstein–Barr virus (EBV) and human papillomavirus (HPV) infection on the tumor microenvironment, we examined the relationship between viral infection status, macrophage migration inhibitory factor (MIF), and tumor-associated macrophages in nasopharyngeal carcinoma (NPC). Methods A tissue microarray containing 150 cores from 90 patients with NPC and six with chronic inflammation was used. EBV and HPV status were detected using in situ hybridization with commercial EBER1 and HPV16/18 probes. Immunofluorescence double staining of MIF, pan-macrophage marker CD68, M1 macrophage marker CD11c, and M2 macrophage marker CD163 were analyzed using the same tissue microarray. The levels of these markers between NPC and inflammation cases and between tumor nests and stroma were compared. Correlations among these markers were analyzed. Results We found EBER1(+) cases in 90% of NPC patients, including 10% EBV/HPV co-infection. M1 macrophages mainly infiltrated the tumor nest, while M2 macrophages infiltrated the tumor stroma. We found a significant positive correlation between EBER1 levels and MIF levels in tumor nests and a significant positive correlation between HPV16/18 and CD11c(+) cell levels in NPC tissues. Conclusions It is suggested that MIF is associated with EBV, and M1 macrophage infiltration is affected by HPV status in NPC.

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“…The binding of MIF to CD74 in melanoma cells promotes PI3K/AKT activation and cell survival. We detected elevated expression of a second MIF receptor, CXCR4, and of another cognate ligand, CXCL12, in the bTIL region; CXCR4 activation leads to expansion of immunosuppressive Tregs (Noe and Mitchell, 2020). CXCR4 is the chemokine receptor most commonly found on cancer cells, and binding to CXLC12 is thought to promote invasive and migratory phenotypes leading to metastasis (Sun et al, 2010).…”

Section: Single-cell Analysis Of Invasive Tumor Reveals Large Scale Gradients In Lineage Immune and Proliferation Markersmentioning

confidence: 98%

The spatial landscape of progression and immunoediting in primary melanoma at single cell resolution

Nirmal

Maliga

Vallius

et al. 2021

Preprint

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Cutaneous melanoma is a highly immunogenic disease, surgically curable at early stages, but life-threatening when metastatic. Here we integrate high-plex imaging, 3D high-resolution microscopy, and spatially-resolved micro-region transcriptomics to study immune evasion and immunoediting in primary melanoma. We find that recurrent cellular neighborhoods involving tumor, immune, and stromal cells change significantly along a progression axis from precursor states to melanoma in situ to invasive tumor. Hallmarks of immunosuppression are detectable by the precursor stage, and when tumors become locally invasive, a consolidated and spatially restricted suppressive environment forms along the tumor-stromal boundary. This environment is established by cytokine gradients that promote expression of MHC-II and IDO1 and by PDL1-expressing macrophages and dendritic cells engaging activated T cells. However, a few mm away, T cells synapse with melanoma cells in fields of tumor regression. Thus, invasion and immunoediting can co-exist within a few millimeters of each other in a single specimen.

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MIF-Dependent Control of Tumor Immunity

Cited by 84 publications

References 197 publications

Circulating MIF Associated With Disease Severity and Clinical Response of Sublingual Immunotherapy in House Dust Mite–Induced Allergic Rhinitis

Circulating MIF Associated With Disease Severity and Clinical Response of Sublingual Immunotherapy in House Dust Mite–Induced Allergic Rhinitis

Influence of Epstein–Barr virus and human papillomavirus infection on macrophage migration inhibitory factor and macrophage polarization in nasopharyngeal carcinoma

The spatial landscape of progression and immunoediting in primary melanoma at single cell resolution

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