S100A9+ MDSC and TAM-mediated EGFR-TKI resistance in lung adenocarcinoma: the role of RELB

Oncotarget
Po-Hao FengKang-Yun Lee

Abstract

Monocytic myeloid-derived suppressor cells (MDSCs), particularly the S100A9+ subset, has been shown initial clinical relevance. However, its role in EGFR-mutated lung adenocarcinoma, especially to EGFR-tyrosine kinase inhibitor (EGFR-TKI) is not clear. In a clinical setting of EGFR mutated lung adenocarcinoma, a role of the MDSC apart from T cell suppression was also investigated. Blood monocytic S100A9+ MDSC counts were higher in lung cancer patients than healthy donors, and were associated with poor treatment response and shorter progression-free survival (PFS). S100A9+ MDSCs in PBMC were well correlated to tumor infiltrating CD68+ and S100A9+ cells, suggesting an origin of TAMs. Patient's MDMs, mostly from S100A9+ MDSC, similar to primary alveolar macrophages from patients, both expressed S100A9 and CD206, attenuated EGFR-TKI cytotoxicity. Microarray analysis identified up-regulation of the RELB signaling genes, confirmed by Western blotting and functionally by RELB knockdown. In conclusion, blood S100A9+ MDSC is a predictor of poor treatment response to EGFR-TKI, possibly via its derived TAMs through activation of the non-canonical NF-κB RELB pathway. Patients with activating EGFR mutation lung adenocarcinoma receiving firs...Continue Reading

References

Aug 2, 2005·Nature Reviews. Immunology·Vincenzo Bronte, Paola Zanovello
Oct 4, 2006·The Journal of Clinical Investigation·Giovanna GallinaVincenzo Bronte
Dec 23, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·E A EisenhauerJ Verweij
Mar 13, 2009·Nature Reviews. Cancer·Johanna A Joyce, Jeffrey W Pollard
Aug 21, 2009·The New England Journal of Medicine·Tony S MokMasahiro Fukuoka
Sep 22, 2010·Nature Immunology·Subhra K Biswas, Alberto Mantovani
Mar 25, 2011·Nature·Trever G BivonaCharles L Sawyers
Jul 20, 2011·Proceedings of the National Academy of Sciences of the United States of America·Hongbo HuShao-Cong Sun
Dec 14, 2011·Genes & Development·Tanaya ShreeJohanna A Joyce
Dec 17, 2011·International Journal of Cancer. Journal International Du Cancer·Fu-Tsai ChungHan-Pin Kuo
Jan 31, 2012·The Lancet Oncology·Rafael RosellUNKNOWN Spanish Lung Cancer Group in collaboration with Groupe Français de Pneumo-Cancérologie and Associazione Italiana Oncologia T
Feb 7, 2012·Immunology·Fei ZhaoFirouzeh Korangy
Feb 7, 2012·Journal of Immunotherapy·Alberto J MonteroSusanna Mandruzzato
Mar 23, 2012·Nature Reviews. Immunology·Dmitry I GabrilovichVincenzo Bronte
May 9, 2012·Virchows Archiv : an International Journal of Pathology·Fotinos-Ioannis D DimitrakopoulosHaralabos P Kalofonos
Sep 8, 2012·American Journal of Respiratory and Critical Care Medicine·Po-Hao FengHan-Pin Kuo
Mar 23, 2013·Cancer Cell·Michele De Palma, Claire E Lewis
Nov 10, 2013·Nature Medicine·Daniela F Quail, Johanna A Joyce
May 9, 2014·Science·Ruth A FranklinMing O Li
May 24, 2014·Nature Reviews. Immunology·Florent Ginhoux, Steffen Jung
Jul 19, 2014·Immunity·Roy Noy, Jeffrey W Pollard
Dec 4, 2014·Nature·Elisa Gomez PerdigueroHans-Reimer Rodewald
Mar 17, 2015·Trends in Immunology·Renato OstuniGioacchino Natoli

❮ Previous
Next ❯

Citations

Oct 10, 2018·Frontiers in Cellular and Infection Microbiology·Nelita du PlessisGerhard Walzl
Jan 11, 2020·Cancer Immunology, Immunotherapy : CII·Mikael RousselJonathan M Irish
Oct 31, 2018·Frontiers in Oncology·Ziwei ZhouHai Hu
Jun 23, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Hou-Qun YingXue-Xin Cheng

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
bronchoalveolar
bronchoalveolar lavage
Confocal microscopy
ELISA
nuclear translocation
transfection
flow
FCS
fluorescence-activated cell sorter

Software Mentioned

GraphPad Prism
FlowJo
Feature extraction
GraphPad
ImageJ
RELB
GeneSpring

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

© 2022 Meta ULC. All rights reserved