Downregulation of the neonatal Fc receptor expression in non-small cell lung cancer tissue is associated with a poor prognosis

Dalloneau, Emilie; Baroukh, Nadine; Mavridis, Konstantinos; Maillet, Agnès; Gueugnon, Fabien; Courty, Yves; Petit, Agnès; Kryza, Thomas; Rio, Maguy Del; Guyétant, Serge; Castaneda, Diana Carolina Cadena; Dhommée, Christine; Arnoult, Christophe; Scorilas, Andreas; Gouilleux-Gruart, Valérie; Heuzé-Vourc’h, Nathalie

doi:10.18632/oncotarget.10074

Cited by 43 publications

(55 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistent with recent analyses of the expression of this receptor in lung cancer [13], the majority of tumor cell lines have very low to undetectable levels of FcRn. Importantly, we demonstrate that the growth of tumors in xenograft models is significantly higher for cells with lower, or knocked down, expression of FcRn.…”

Section: Introductionsupporting

confidence: 85%

“…Further, the correlation of FcRn expression levels at the tumor site with favorable prognosis has been proposed to relate to the function of this receptor in hematopoietic cells [13]. However, in addition to the immunological activity of FcRn involving IgG interactions and antigen presentation [25–27], our studies demonstrate that the levels of this receptor within the tumor cells themselves modulate cancerous growth by regulating albumin accumulation.…”

Section: Discussionmentioning

confidence: 71%

See 1 more Smart Citation

Loss of expression of the recycling receptor, FcRn, promotes tumor cell growth by increasing albumin consumption

Swiercz

Khare

et al. 2016

Oncotarget

View full text Add to dashboard Cite

Tumor cells rely on high concentrations of amino acids to support their growth and proliferation. Although increased macropinocytic uptake and lysosomal degradation of the most abundant serum protein, albumin, in Ras-transformed cells can meet these demands, it is not understood how the majority of tumor cells that express wild type Ras achieve this. In the current study we reveal that the neonatal Fc receptor, FcRn, regulates tumor cell proliferation through the ability to recycle its ligand, albumin. By contrast with normal epithelial cells, we show that human FcRn is present at very low or undetectable levels in the majority of tumor cell lines analyzed. Remarkably, shRNA-mediated ablation of FcRn expression in an FcRn-positive tumor cell line results in a substantial growth increase of tumor xenografts, whereas enforced expression of this receptor by lentiviral transduction has the reverse effect. Moreover, intracellular albumin and glutamate levels are increased by the loss of FcRn-mediated recycling of albumin, combined with hypoalbuminemia in tumor-bearing mice. These studies identify a novel role for FcRn as a suppressor of tumor growth and have implications for the use of this receptor as a prognostic indicator and therapeutic target.

show abstract

Section: Introductionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 71%

Loss of expression of the recycling receptor, FcRn, promotes tumor cell growth by increasing albumin consumption

Swiercz

Khare

et al. 2016

Oncotarget

View full text Add to dashboard Cite

show abstract

“…The density of FcRn-expressed DCs was correlated with CD8 + T-cell number and predicted improved prognosis in human colorectal carcinoma. Second, we reported FcRn mRNA and protein levels in both lung cancerous tissue and non-cancerous tissue associated with favorable prognosis in non-small cell lung cancer ( 13 ). Third, studies involving neoplastic cells expressing different levels of FcRn showed that FcRn-mediated recycling of albumin reduced tumor cell growth and proliferation ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

Lack of FcRn Impairs Natural Killer Cell Development and Functions in the Tumor Microenvironment

et al. 2018

Self Cite

View full text Add to dashboard Cite

The neonatal Fc receptor (FcRn) is responsible for the recycling and transcytosis of IgG and albumin. FcRn level was found altered in cancer tissues and implicated in tumor immunosurveillance and neoplastic cell growth. However, the consequences of FcRn down-regulation in the anti-tumor immune response are not fully elucidated. By using the B16F10 experimental lung metastasis model in an FcRn-deficient microenvironment (FcRn−/− mice), we found lung metastasis associated with an abnormal natural killer (NK) cell phenotype. In FcRn−/− mice, NK cells were immature, as shown by their surface marker profile and their decreased ability to degranulate and synthesize interferon γ after chemical and IL-2 or IL-12, IL-15 and IL-18 activation. These new findings support the critical role of FcRn downregulation in the tumor microenvironment in anti-tumor immunity, via NK cell maturation and activation.

show abstract

“…FcRn also plays an important role in adaptive immunity. (12,(20)(21)(22)(23)(24) Studies in dendritic cells have established that FcRn is necessary for trafficking antigen-antibody complexes for degradation as well as presentation on MHCII. (10,20,25,26) Furthermore, studies have shown that when FcRn is absent, dendritic cells cannot present antigen for antigen presentation.…”

Section: Introductionmentioning

confidence: 99%

Podocyte-specific knockout of the neonatal Fc receptor (FcRn) results in differential protection depending on the model of immune-mediated kidney disease

Dylewski

Tonsawan

Garcia

et al. 2020

Preprint

View full text Add to dashboard Cite

Podocytes have been proposed to be antigen presenting cells (APCs). In traditional APCs, the neonatal Fc receptor (FcRn) is required for antigen presentation and global knockout of FcRn protects against immune-mediated kidney disease. Since podocytes express FcRn, we sought to determine whether the absence of podocyte FcRn ameliorates immune-mediated disease. We examined MHCII and costimulatory markers expression in cultured wild type (WT) and FcRn knockout (KO) podocytes. Interferon gamma (IFN) induced MHCII expression in both WT and KO podocytes but did not change CD80 expression. Neither WT nor KO expressed CD86 or inducible costimulatory ligand (ICOSL) at baseline or with IFN Using an antigen presentation assay, WT podocytes but not KO treated with immune complexes induced a modest increase in IL-2. Induction of the anti-glomerular basement membrane (anti-GBM) model resulted in a significant decrease in glomerular crescents in podocyte-specific FcRn knockout mouse (podFcRn KO) versus controls but the overall percentage of crescents was low. To examine the effects of the podocyte-specific FcRn knockout in a model with a longer autologous phase, we used the nephrotoxic serum nephritis (NTS) model. We found that the podFcRn KO mice had significantly reduced crescent formation and glomerulosclerosis compared to control mice. This study demonstrates that lack of podocyte FcRn is protective in immune mediated kidney disease that is dependent on an autologous phase. This study also highlights the difference between the anti-GBM model and NTS model of disease.

show abstract

Downregulation of the neonatal Fc receptor expression in non-small cell lung cancer tissue is associated with a poor prognosis

Cited by 43 publications

References 42 publications

Loss of expression of the recycling receptor, FcRn, promotes tumor cell growth by increasing albumin consumption

Loss of expression of the recycling receptor, FcRn, promotes tumor cell growth by increasing albumin consumption

Lack of FcRn Impairs Natural Killer Cell Development and Functions in the Tumor Microenvironment

Podocyte-specific knockout of the neonatal Fc receptor (FcRn) results in differential protection depending on the model of immune-mediated kidney disease

Contact Info

Product

Resources

About