Dataset Information

Immunoproteomics of Lymph Node T-cells in Bladder Cancer

ABSTRACT: The immune-suppressive features often possessed by invasive tumors hamper effective anti-tumor immunity. In this context, tumor-infiltrating regulatory T cells (Tregs) have been widely implied, principally as unwanted suppressors of anti-tumor immune responses. However, while many studies have focused on tumor-infiltrating Tregs, the function and signaling of Tregs in tumor-associated lymph nodes is largely unknown. In this study, we set out to clarify how immune signaling in lymph nodes is impacted by its contact to the tumour. Because muscle-invasive urothelial bladder cancer (MIBC) represent an immunogenic cancer were Tregs are accumulated and sentinel nodes (SNs) can be efficiently detected, we explored the protein expression of T-cells in SNs and non-SNs of MIBC patients. Proteomic analysis of Tregs and effector T-cells in SN and non-draining lymph nodes found SN-Tregs in MIBC patients to up-regulate growth and immune signaling pathways, the cytokine IL-16 being central in the signaling network. Experimental validation showed that in Tregs, tumoral factors increase IL-16 processing into bioactive forms and increase FOXP3 expression. In conclusion, altered IL-16 processing caused by tumour-released factors stimulate expansion of SN-Tregs in MIBC, creating an immunosuppressive environment and contributing to immune escape.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): T Cell, Lymph Node, Blood

SUBMITTER: Michael Mints

LAB HEAD: Ola Winqvist

PROVIDER: PXD009569 | Pride | 2020-09-09

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20140611_04_Q2_Mintz_PBMC_Treg.raw	Raw
	20140611_05_Q2_Mintz_SN_Treg.raw	Raw
	20140611_06_Q2_Mintz_nSN_Treg.raw	Raw
	20140611_07_Q2_Mintz_PBMC_Teff.raw	Raw
	20140611_08_Q2_Mintz_TIL_Teff.raw	Raw

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Publications

IL-16 processing in sentinel node regulatory T cells is a factor in bladder cancer immunity.

Krantz David D Mints Michael M Winerdal Malin M Riklund Katrine K Rutishauser Dorothea D Zubarev Roman R Zirakhzadeh Amir Ali AA Alamdari Farhood F Johansson Markus M Sherif Amir A Winqvist Ola O

Scandinavian journal of immunology 20200830 6

In the effort of developing new immunotherapies, the sentinel node (SN) has proven a promising source from which to harness an effective antitumour T cell response. However, tumour immune escape, a process in which regulatory T cells (Tregs) play a central role, remains a major limiting factor. Therefore, there is a clear need to increase the knowledge of Treg function and signalling in sentinel nodes. Here, we set out to explore whether the proteome in SN-resident T cells is altered by the tumo ...[more]

PMID: 32862475

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