PXD003136

PXD003136 is an original dataset announced via ProteomeXchange.

Title	Interleukin-6 induced ‘acute’ response promotes Th1 anti-tumor immunity in cryo-thermal therapy: shotgun proteomics
Description	Cryo-thermal therapy has been proven to be a promising novel systemic strategy for advanced breast cancer, resulting in higher incidence of tumor regression and enhanced remission of metastasis. The mechanism by which such strategy boosts the anti-tumor activity remains unclear. To gain a system-wide understanding of the anti-tumor response, here we utilized a spontaneous metastatic mouse model and quantitative proteomics to compare the N-glycoproteome changes following treatment or not in 94 serum samples over 8 time points. We quantified 231 high confident N-glycosylated serum proteins in total using iTRAQ labeling shotgun proteomic. 53 of them showed significant regulatory patterns over time course, in which we identified acute phase response as the most enhanced pathway and markedly distinguished in the hierarchical proteome profile. We therefore investigated the function of acute response in tumoricidal effect using quantitative parallel reaction monitoring proteomics and flow cytometry upon 23 out of 53 significant proteins. We found that cryo-thermal therapy reshaped the tumor chronic inflammatory microenvironment to an ‘acute’ phenotype, accompanying ‘acute’ and markedly high expression of acute phase proteins and their key upstream regulator -interleukin 6. Such IL-6 mediated ‘acute’ phenotype drove the tumor site from a Th2 immunosuppressive, pro-tumorigenic to a Th1 immunostimulatory, tumouricidal phenotype, inducing a switch from IL-4 and Treg-promoting ICOSL expression to Th1-promoting IFN –γand IL-12 production, skewing to complement system activation and CD86+MHCII+ dendritic cells maturation, and enhancing the proliferation of Th1 memory cells. We also found an increased production of tumor metastatic inhibitors under such ‘acute’ environment, favoring the anti-metastatic effect. In this study, we revealed that IL-6 mediated ‘acute’ inflammatory profile played a key role to suppress immunosuppression and wake up the anti-tumor activity, recovering host metabolism and physiology. This could guide us a better understanding to improve this cancer treatment for better therapeutic effect.
HostingRepository	PRIDE
AnnounceDate	2016-05-12
AnnouncementXML	Submission_2016-05-12_00:39:54.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	ting xue
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iTRAQ8plex-116 reporter+balance reagent acylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2015-11-03 01:45:57	ID requested
⏵ 1	2016-05-12 00:39:57	announced

Xue T, Liu P, Zhou Y, Liu K, Yang L, Moritz RL, Yan W, Xu LX, Interleukin-6 Induced "Acute" Phenotypic Microenvironment Promotes Th1 Anti-Tumor Immunity in Cryo-Thermal Therapy Revealed By Shotgun and Parallel Reaction Monitoring Proteomics. Theranostics, 6(6):773-94(2016) [pubmed]

submitter keyword: acute phase response, Th1 anti-tumor immunity, cryo-thermal therapy, interleukin-6, parallel reaction monitoring

Lisa X.Xu
contact affiliation	Bioheat and mass transfer laboratory, Med-X Research Institute, Shanghai Jiao Tong University
contact email	lisaxu@sjtu.edu.cn
lab head
ting xue
contact affiliation	shanghai jiaotong university
contact email	xueting221314@126.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD003136
     1. Label: PRIDE project
     2. Name: Interleukin-6 induced ‘acute’ response promotes Th1 anti-tumor immunity in cryo-thermal therapy: shotgun proteomics