Dataset Information

Proteomic analysis of 293T-MDSCs

ABSTRACT: In order to analyse the 293T-MDSCs proteome in a large-scale format, we used a fractionation approach which combines peptide chromatographic fractionation strategies coupled to mass spectrometry.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture, Myeloid Suppressor Cell

DISEASE(S): Melanoma

SUBMITTER: Enrique SantamarÃa

LAB HEAD: Enrique Santamaria

PROVIDER: PXD001106 | Pride | 2016-07-07

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	A10TheraiTRAQ1-02052014-2.wiff	Wiff
	A10TheraiTRAQ1-02052014-2.wiff.scan	Wiff
	A11TheraiTRAQ1-02052014-3.wiff	Wiff
	A11TheraiTRAQ1-02052014-3.wiff.scan	Wiff
	A12TheraiTRAQ1-02052014-4.wiff	Wiff

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Publications

A highly efficient tumor-infiltrating MDSC differentiation system for discovery of anti-neoplastic targets, which circumvents the need for tumor establishment in mice.

Liechtenstein Therese T Perez-Janices Noemi N Gato Maria M Caliendo Fabio F Kochan Grazyna G Blanco-Luquin Idoia I Van der Jeught Kevin K Arce Frederick F Guerrero-Setas David D Fernandez-Irigoyen Joaquin J Santamaria Enrique E Breckpot Karine K Escors David D

Oncotarget 20140901 17

Myeloid-derived suppressor cells (MDSCs) exhibit potent immunosuppressive activities in cancer. MDSCs infiltrate tumors and strongly inhibit cancer-specific cytotoxic T cells. Their mechanism of differentiation and identification of MDSC-specific therapeutic targets are major areas of interest. We have devised a highly efficient and rapid method to produce very large numbers of melanoma-infiltrating MDSCs ex vivo without inducing tumors in mice. These MDSCs were used to study their differentiati ...[more]

PMID: 25151659

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Project description:Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that accumulate in the tumor microenvironment of most cancer patients. There MDSCs suppress both adaptive and innate immune responses, hindering immunotherapies. Moreover, many cancers are accompanied by inflammation, a processes that further intensifies MDSC suppressive activity, causing aggressive tumor progression and metastasis. MDSCs collected from tumor-bearing mice profusely release nano-scale membrane-bound extracellular vesicles, called exosomes, which carry biologically active proteins between cells and contribute directly to the immune suppressive functions of MDSC. Many studies on other cell types have shown that exosomes may also carry microRNAs (miRNAs) and messenger RNAs (mRNAs) which can also be transferred to surrounding and distant cells. However, to the best of our knowledge, the miRNA and mRNA cargo of MDSC-derived exosomes has not yet been interrogated. This study aims to identify and quantify the cargo of MDSC and their immunosuppressive exosomes to gather knowledge that can offer insights on the mechanisms by which MDSCs contribute to immune suppression, focusing on the role of exosomes as intercellular communication mediators in the tumor microenvironment. In order to achieve our objective a well-established mouse model based on a conventional mammary carcinoma (4T1 cells) and heightened inflammation (4T1 transduced to express the cytokine interleukin-1b) was used. We provide evidence that MDSC-derived exosomes carry proteins, mRNAs and miRNAs. Relative quantitation demonstrated quantitative differences between the exosome cargo and the cargo of their parental cells, supporting the hypothesis that selective loading into the exosomes is possible. Additionally, quantitative and functional analyses of the exosome cargo generated under conventional and heightened inflammation conditions are consistent with clinical observations that inflammation is linked to cancer development.