Dataset Information

Pro-inflammatory Cytokines Alter the Immunopeptidome Landscape by Modulation of HLA-B Expression.

ABSTRACT: Antigen presentation on HLA molecules is a major mechanism by which the immune system monitors self and non-self-recognition. Importantly, HLA-I presentation has gained much attention through its role in eliciting anti-tumor immunity. Several determinants controlling the peptides presented on HLA have been uncovered, mainly through the study of model substrates and large-scale immunopeptidome analyses. These determinants include the relative abundances of proteins in the cell, the stability or turnover rate of these proteins and the binding affinities of a given peptide to the HLA haplotypes found in a cell. However, the regulatory principles involved in selection and regulation of specific antigens in response to tumor pro-inflammatory signals remain largely unknown. Here, we chose to examine the effect that TNF? and IFN? stimulation may exert on the immunopeptidome landscape of lung cancer cells. We show that the expression of many of the proteins involved in the class I antigen presentation pathway are changed by pro-inflammatory cytokines. Further, we could show that increased expression of the HLA-B allomorph drives a significant change in HLA-bound antigens, independently of the significant changes observed in the cellular proteome. Finally, we observed increased HLA-B levels in correlation with tumor infiltration across the TCGA lung cancer cohorts. Taken together, our results suggest that the immunopeptidome landscape should be examined in the context of anti-tumor immunity whereby signals in the microenvironment may be critical in shaping and modulating this important aspect of host-tumor interactions.

SUBMITTER: Javitt A

PROVIDER: S-EPMC6387973 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Pro-inflammatory Cytokines Alter the Immunopeptidome Landscape by Modulation of HLA-B Expression.

Javitt Aaron A Barnea Eilon E Kramer Matthias P MP Wolf-Levy Hila H Levin Yishai Y Admon Arie A Merbl Yifat Y

Frontiers in immunology 20190218

Antigen presentation on HLA molecules is a major mechanism by which the immune system monitors self and non-self-recognition. Importantly, HLA-I presentation has gained much attention through its role in eliciting anti-tumor immunity. Several determinants controlling the peptides presented on HLA have been uncovered, mainly through the study of model substrates and large-scale immunopeptidome analyses. These determinants include the relative abundances of proteins in the cell, the stability or t ...[more]

PMID: 30833945

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Project description:The well-recognized cell phenotypic heterogeneity in tumors is a great challenge for cancer treatment. Dynamic interconversion and movement within a spectrum of different cell phenotypes (cellular plasticity) with the acquisition of specific cell functions is a fascinating biological puzzle, that represent an additional difficulty for cancer treatment and novel therapies development. The understanding of the molecular mechanisms responsible for moving or stabilizing tumor cells within this spectrum of variable states constitutes a valuable tool to overcome these challenges. In particular, cell transitions between epithelial and mesenchymal phenotypes (EMT-MET) and de-and trans-differentiation processes are relevant, since it has been shown that they confer invasiveness, drug resistance, and metastatic ability, due to the simultaneous acquisition of stem-like cell properties. Multiple drivers participate in these cell conversions events. In particular, cellular senescence and senescence-associated soluble factors have been shown to unveil stem-like cell properties and cell plasticity. By modulating gradually the composition of their secretome and the time of exposure, senescent cells may have differential effect not only on tumor cells but also on surrounding cells. Intriguingly, tumor cells that scape from senescence acquire stem-like cell properties and aggressiveness. The reinforcement of senescence and inflammation by soluble factors and the participation of immune cells may provide a dynamic milieu having varied effects on cell transitions, reprogramming, plasticity, stemness and therefore heterogeneity. This will confer different epithelial/mesenchymal traits (hybrid phenotype) and stem-like cell properties, combinations of which, in a particular cell context, could be responsible for different cellular functions during cancer progression (survival, migration, invasion, colonization or proliferation). Additionally, cooperative behavior between cell subpopulations with different phenotypes/stemness functions could also modulate their cellular plasticity. Here, we will discuss the role of senescence and senescence-associated pro-inflammatory cytokines on the induction of cellular plasticity, their effect role in establishing particular states within this spectrum of cell phenotypes and how this is accompanied by stem-like cell properties that, as the epithelial transitions, may also have a continuum of characteristics providing tumor cells with functional adaptability specifically useful in the different stages of carcinogenesis.

Dataset Information

Pro-inflammatory Cytokines Alter the Immunopeptidome Landscape by Modulation of HLA-B Expression.

Publications

Pro-inflammatory Cytokines Alter the Immunopeptidome Landscape by Modulation of HLA-B Expression.

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