Targeting CXCR4 reverts the suppressive activity of T-regulatory cells in renal cancer

Oncotarget
Sara SantagataStefania Scala

Abstract

With the intent to identify biomarkers in renal cell carcinoma (RCC) the functional status of T-regulatory cells (Tregs) was investigated in primary RCC. Tregs were isolated from tumoral-(TT), peritumoral tissue-(PT) and peripheral blood-(PB) of 42 primary RCC patients and function evaluated through effector T cells (Teff) proliferation, cytokines release and demethylation of Treg Specific Region (TSDR). The highest value of Tregs was detected in TT with the uppermost amount of effector-Tregs-(CD4(+)CD25(hi)FOXP3(hi)CD45RA(-)). PB-RCC Tregs efficiently suppress Teff proliferation compared to healthy donor (HD)-Tregs and, at the intrapatient evaluation, TT-derived Tregs were the most suppressive. Higher demethylation TSDR was detected in TT- and PB-RCC Tregs vs HD-Tregs (P <0,001). CXCR4 is highly expressed on Tregs, thus we wished to modulate Tregs function through CXCR4 inhibition. CXCR4 antagonism, elicited by a new peptidic antagonist, Peptide-R29, efficiently reversed Tregs suppression of Teff proliferation. Thus Tregs functional evaluation precisely reflects Tregs status and may be a reliable biomarker of tumoral immune response. In addition, treatment with CXCR4 antagonist, impairing Tregs function, could improve the anti...Continue Reading

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Citations

Jun 26, 2018·International Immunology·Kanako ShimizuShin-Ichiro Fujii
Apr 9, 2020·Vaccines·Stefania ScalaElena Monica Borroni
Mar 20, 2020·Current Pharmaceutical Design·Zhi-Xiang YuanJuchun Lin
Aug 15, 2018·Annals of Nuclear Medicine·Malte KircherConstantin Lapa
Oct 27, 2018·Frontiers in Immunology·Francesca FerrandinoMaria Pia Felli
Mar 13, 2019·Cancer Science·Shichao ZhangZhu Zeng
Dec 6, 2018·Journal of Experimental & Clinical Cancer Research : CR·Anna Maria TrottaStefania Scala
Feb 26, 2019·Frontiers in Immunology·Nicole Salazar, Brian A Zabel
Oct 30, 2019·Journal of Experimental & Clinical Cancer Research : CR·Crescenzo D'AlterioStefania Scala
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Jan 10, 2019·Frontiers in Immunology·Franziska EckertStephan M Huber
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Jan 21, 2021·International Journal of Molecular Sciences·Jan KorbeckiIrena Baranowska-Bosiacka
Nov 7, 2020·Circulation Research·Wesley Tyler AbplanalpStefanie Dimmeler
Mar 8, 2021·BMC Nephrology·Colleen S Curran, Jeffrey B Kopp
Mar 28, 2021·Blood Reviews·José Carlos Jaime-PérezDavid Gómez-Almaguer
Apr 30, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Minglu ZhouYuan Huang
Jun 11, 2021·Clinical and Experimental Nephrology·Milena Potić FloranovićLjubinka Janković Veličković
Jun 7, 2021·Neoplasia : an International Journal for Oncology Research·Gaurav KumarChinthalapally V Rao
Sep 17, 2021·Current Cancer Drug Targets·Anna KasperskaŁukasz Szylber

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Methods Mentioned

BETA
ELISA
biopsy
acetylation
biopsies
flow cytometry
FACS

Software Mentioned

FacsDiva

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