Cancer associated fibroblasts sculpt tumour microenvironment by recruiting monocytes and inducing immunosuppressive PD-1+ TAMs

Scientific Reports
Betul Gok YavuzDicle Guc

Abstract

Fibroblasts turn into cancer associated fibroblasts (CAFs) in the tumour microenvironment. CAFs have recently attracted attention for their function as a regulator of immune cell recruitment and function in addition to their tumour-promoting roles. In this study, we aimed to determine the role of CAFs on monocyte recruitment and macrophage polarization in breast cancer. CAFs, which were α-SMA expressing fibroblasts in contrast to normal fibroblasts (NFs), effectively recruited monocytes. Recruitment of monocytes by CAFs might be mediated by monocyte chemotactic protein-1 (MCP-1) as well as stromal cell-derived factor-1 (SDF-1) cytokines. CAFs differentiated the recruited monocytes into M2-like macrophages which are capable of exerting their immunosuppressive roles via the PD-1 axis. CAF-educated monocytes exhibited strong immune suppression unlike NF-educated monocytes and enhanced the motility/invasion of breast cancer cells in addition to increasing the expressions of epithelial-mesenchymal transition (EMT)-related genes and vimentin protein in cancer cells. CAF-educated M1 macrophages displayed increased expression of M2 markers and production of anti-inflammatory cytokine IL-10 in contrast to decreased production of pro-inf...Continue Reading

References

Mar 7, 2001·Lancet·F Balkwill, A Mantovani
Mar 9, 2002·Science·Sena J LeeMichel C Nussenzweig
Dec 6, 2002·Journal of Mammary Gland Biology and Neoplasia·Elaine Y LinJeffrey W Pollard
Jan 7, 2004·Nature Reviews. Cancer·Jeffrey W Pollard
Nov 9, 2004·Trends in Immunology·Alberto MantovaniMassimo Locati
Jul 16, 2005·Blood·Julien Y BertrandIsabelle Godin
Nov 22, 2005·Clinical and Experimental Immunology·F PorcherayG Gras
Mar 8, 2006·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Antonio SicaPaola Allavena
Nov 21, 2007·Cancer Biology & Therapy·Akira Orimo, Robert A Weinberg
Sep 9, 2008·International Journal of Cancer. Journal International Du Cancer·Olivier De WeverMarc Bracke
Nov 26, 2008·Nature Reviews. Immunology·David M Mosser, Justin P Edwards
Jan 7, 2009·Current Opinion in Oncology·Mikael J Pittet
May 21, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Beverly A Teicher, Simon P Fricker
Jun 10, 2011·Nature·Bin-Zhi QianJeffrey W Pollard
Nov 15, 2011·Journal of Immunological Methods·C A AmbarusD L P Baeten
Jan 3, 2012·Seminars in Cancer Biology·Frances R Balkwill, Alberto Mantovani
Mar 2, 2012·The Journal of Clinical Investigation·Antonio Sica, Alberto Mantovani
Mar 24, 2012·Science·Christian SchulzFrederic Geissmann
Jun 5, 2012·The New England Journal of Medicine·Suzanne L TopalianMario Sznol
Oct 2, 2012·Molecular Cancer Research : MCR·George S KaragiannisEleftherios P Diamandis
Jan 19, 2013·Science·Lisa M CoussensA Karolina Palucka
Apr 27, 2013·Nature·Thomas A WynnJeffrey W Pollard
Jan 11, 2014·Seminars in Cancer Biology·James Harper, Richard C A Sainson
Mar 19, 2014·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Susanne M OhlssonThomas Hellmark
May 9, 2014·Science·Ruth A FranklinMing O Li
Jul 19, 2014·Immunity·Roy Noy, Jeffrey W Pollard
Dec 3, 2014·The American Journal of Pathology·Kenta KambaraYuichi Hattori
Aug 6, 2015·Breast Cancer Research : BCR·Sofia SousaJorma A Määttä
Jan 1, 2015·Arthritis Research & Therapy·Gregor OlmesChristoph Daniel

❮ Previous
Next ❯

Citations

Oct 24, 2019·Journal of Cellular and Molecular Medicine·Yuanyuan AnQing Yang
Apr 7, 2020·Expert Opinion on Therapeutic Targets·Rosamaria LappanoErnestina Marianna De Francesco
Apr 9, 2020·Cell Communication and Signaling : CCS·Roghayyeh BaghbanPeyman Zare
May 10, 2020·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Yangguang XuChi Zhang
Sep 23, 2020·International Journal of Molecular Sciences·Issraa ShoucairCathie Garnis
Jan 21, 2020·Journal of Cellular and Molecular Medicine·Zeru FengXikun Zhou
May 4, 2020·Molecular Cancer·Xueping WangLiwu Fu
Aug 28, 2020·Frontiers in Cell and Developmental Biology·Yanfei YangXiawei Wei
Jan 14, 2021·Biomaterials Science·Kanishka FernandoEliza Li Shan Fong
Oct 7, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Fakhrossadat EmamiSimmyung Yook
Oct 31, 2020·Signal Transduction and Targeted Therapy·Ashenafi Bulle, Kian-Huat Lim
Feb 12, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Jaehyun KimYong-Hee Kim
Jan 6, 2021·Journal of Mammary Gland Biology and Neoplasia·María Belén GiorelloNorma Alejandra Chasseing
Oct 30, 2020·Cancers·Kévin LouaultYves A DeClerck
Feb 26, 2021·Frontiers in Immunology·Russell FoxallMark S Cragg
Apr 13, 2021·Frontiers in Oncology·Benedetta ApollonioAlan G Ramsay
Apr 23, 2021·Biochemical Pharmacology·Soumeya AbedAnthony F Rullo
May 6, 2021·International Journal of Molecular Sciences·Vicenç Ruiz de PorrasAlbert Font
Jun 5, 2021·Advanced Drug Delivery Reviews·Leon Jia Wei TangEliza Li Shan Fong
Jul 25, 2021·Cancers·Ana Maia, Stefan Wiemann
Aug 3, 2021·Frontiers in Cell and Developmental Biology·Stefano Piatto ClericiCarmen Veríssima Ferreira-Halder

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
PCR
ELISA
enzyme-linked immunosorbent assays
biosensor

Software Mentioned

SPSS Statistics

Related Concepts