Skip to main content
Key Specialties
Anesthesiology Cardiology Dermatology Diabetology Endocrinology Gastroenterology General Medicine Geriatrics Hematology Infectious Diseases Internal Medicine Nephrology Neurology Obstetrics and Gynecology Oncology Pediatrics Psychiatry Radiology Respiratory Medicine Rheumatology Surgery Urology
Congress Coverage
2024 ESMO Congress 2024 ERS Congress 2024 EASD Congress 2024 ESC Congress 2024 EAN Congress 2024 ASCO Annual Meeting 2024 ACC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on modern management of frailty

LIVE: Thursday 17th October 2024, 18:00-19:30 (CEST)

Frailty has a significant impact on health and wellbeing, especially in older adults. Join our experts to understand the factors that contribute to the development of frailty and find out how to manage the condition and reduce the risk of disability, dependency, and mortality.
ADVANCED SEARCH
Log in
Top
Clinical and Translational Oncology

06-09-2024 | Prostate Cancer | RESEARCH ARTICLE

TET3 is expressed in prostate cancer tumor-associated macrophages and is associated with anti-androgen resistance

Authors: Qiu-ju Wei, Hai-qi Liang, Yao-wen Liang, Zu-xin Huang

Published in: Clinical and Translational Oncology

Login to get access

Abstract

Purpose

The aim of this study is to investigate the expression of TET3 in prostate cancer and its effect on the efficacy of anti-androgen therapy (ADT).

Methods

The expression of TET3 in 1965 cases of prostate cancer and 493 cases of normal prostate tissues were analyzed. The CIBERSORT algorithm evaluated the abundance of 22 tumor-infiltrating immune cells in 497 prostate cancers. Subsequently, the expression of TET3 in prostate cancer TAMs was analyzed using 21,292 cells from single-cell RNA sequencing (scRNAseq). In addition, the trajectory of the differentiation process was reconstructed based on pseudotime analysis. Sensitivity prediction of prostate cancers to ADT was evaluated based on GDSC2 and CTRP databases. Another dataset GSE111177 was employed for further analysis.

Results

TET3 was over-expressed in prostate cancer, and the expression of TET3 in metastatic prostate cancer was higher than that in non-metastatic prostate cancer. The scRNAseq analysis of prostate cancer showed that TET3 was mainly expressed in TAM. TET3 expressed in early and active TAMs, with the activation of signaling pathways such as energy metabolism, cell communication, and cytokine production. Prostate cancer in TET3 high expression group was more sensitive to ADT drugs such as Bicalutamide and AZD3514, and was also more sensitive to chemotherapy drugs such as Cyclophosphamide, Paclitaxel, and Vincristine, and MAPK pathway inhibitors of Docetaxel and Dabrafenib.

Conclusions

The efficacy of ADT in prostate cancer is related to the expression of TET3 in TAMs, and TET3 may be a potential therapeutic target for coordinating ADT.
Appendix
Available only for authorised users
Literature
1.
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49.CrossRefPubMed
2.
Bill-Axelson A, Holmberg L, Garmo H, Taari K, Busch C, Nordling S, et al. Radical prostatectomy or watchful waiting in prostate cancer - 29-year follow-up. N Engl J Med. 2018;379:2319–29.CrossRefPubMed
3.
Sweeney CJ, Martin AJ, Stockler MR, Begbie S, Cheung L, Chi KN, et al. Testosterone suppression plus enzalutamide versus testosterone suppression plus standard antiandrogen therapy for metastatic hormone-sensitive prostate cancer (ENZAMET): an international, open-label, randomised, phase 3 trial. Lancet Oncol. 2023;24:323–34.CrossRefPubMed
4.
Wang H, Li N, Liu Q, Guo J, Pan Q, Cheng B, et al. Antiandrogen treatment induces stromal cell reprogramming to promote castration resistance in prostate cancer. Cancer Cell. 2023;41:1345-62.e9.CrossRefPubMed
5.
6.
7.
8.
Yeaton A, Cayanan G, Loghavi S, Dolgalev I, Leddin EM, Loo CE, et al. The impact of inflammation-induced tumor plasticity during myeloid transformation. Cancer Discov. 2022;12:2392–413.CrossRefPubMedPubMedCentral
9.
Li X, Zhang Q, Ding Y, Liu Y, Zhao D, Zhao K, et al. Methyltransferase Dnmt3a upregulates HDAC9 to deacetylate the kinase TBK1 for activation of antiviral innate immunity. Nat Immunol. 2016;17:806–15.CrossRefPubMed
10.
Duforestel M, Nadaradjane A, Bougras-Cartron G, Briand J, Olivier C, Frenel JS, et al. Glyphosate primes mammary cells for tumorigenesis by reprogramming the epigenome in a TET3-dependent manner. Front Genet. 2019;10:885.CrossRefPubMedPubMedCentral
11.
Ciesielski P, Jóźwiak P, Forma E, Krześlak A. TET3- and OGT-dependent expression of genes involved in epithelial-mesenchymal transition in endometrial cancer. Int J Mol Sci. 2021;22:13239.CrossRefPubMedPubMedCentral
12.
Du Y, Li R, Fu D, Zhang B, Cui A, Shao Y, et al. Multi-omics technologies and molecular biomarkers in brain tumor-related epilepsy. CNS Neurosci Ther. 2024;30: e14717.CrossRefPubMedPubMedCentral
13.
14.
Uhlén M, Fagerberg L, Hallström BM, Lindskog C, Oksvold P, Mardinoglu A, et al. Proteomics. Tissue-based map of the human proteome. Science. 2015;347:1260419.CrossRefPubMed
15.
Sui S, An X, Xu C, Li Z, Hua Y, Huang G, et al. An immune cell infiltration-based immune score model predicts prognosis and chemotherapy effects in breast cancer. Theranostics. 2020;10:11938–49.CrossRefPubMedPubMedCentral
16.
Yoshihara K, Shahmoradgoli M, Martínez E, Vegesna R, Kim H, Torres-Garcia W, et al. Inferring tumour purity and stromal and immune cell admixture from expression data. Nat Commun. 2013;4:2612.CrossRefPubMed
17.
Dong B, Miao J, Wang Y, Luo W, Ji Z, Lai H, et al. Single-cell analysis supports a luminal-neuroendocrine transdifferentiation in human prostate cancer. Commun Biol. 2020;3:778.CrossRefPubMedPubMedCentral
18.
Hao Y, Hao S, Andersen-Nissen E, Mauck WM 3rd, Zheng S, Butler A, et al. Integrated analysis of multimodal single-cell data. Cell. 2021;184:3573-87.e29.CrossRefPubMedPubMedCentral
19.
Trapnell C, Cacchiarelli D, Grimsby J, Pokharel P, Li S, Morse M, et al. The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells. Nat Biotechnol. 2014;32:381–6.CrossRefPubMedPubMedCentral
20.
Thomas PD, Ebert D, Muruganujan A, Mushayahama T, Albou LP, Mi H. PANTHER: Making genome-scale phylogenetics accessible to all. Protein Sci. 2022;31:8–22.CrossRefPubMed
21.
Wu T, Hu E, Xu S, Chen M, Guo P, Dai Z, et al. clusterProfiler 4.0: A universal enrichment tool for interpreting omics data. Innovation. 2021;2:100141.PubMedPubMedCentral
22.
Sharma NV, Pellegrini KL, Ouellet V, Giuste FO, Ramalingam S, Watanabe K, et al. Identification of the transcription factor relationships associated with androgen deprivation therapy response and metastatic progression in prostate cancer. Cancers. 2018;10:379.CrossRefPubMedPubMedCentral
23.
Ma Z, Zhang W, Dong B, Xin Z, Ji Y, Su R, et al. Docetaxel remodels prostate cancer immune microenvironment and enhances checkpoint inhibitor-based immunotherapy. Theranostics. 2022;12:4965–79.CrossRefPubMedPubMedCentral
24.
Guggenberger F, van de Werken HJG, Erb HHH, Cappellano G, Trattnig K, Handle F, et al. Fractionated radiation of primary prostate basal cells results in downplay of interferon stem cell and cell cycle checkpoint signatures. Eur Urol. 2018;74:847–9.CrossRefPubMed
25.
Gao J, Ward JF, Pettaway CA, Shi LZ, Subudhi SK, Vence LM, et al. VISTA is an inhibitory immune checkpoint that is increased after ipilimumab therapy in patients with prostate cancer. Nat Med. 2017;23:551–5.CrossRefPubMedPubMedCentral
26.
Xu Y, Du Y, Zheng Q, Zhou T, Ye B, Wu Y, et al. Identification of ferroptosis-related prognostic signature and subtypes related to the immune microenvironment for breast cancer patients receiving neoadjuvant chemotherapy. Front Immunol. 2022;13: 895110.CrossRefPubMedPubMedCentral
27.
Pastor WA, Aravind L, Rao A. TETonic shift: biological roles of TET proteins in DNA demethylation and transcription. Nat Rev Mol Cell Biol. 2013;14:341–56.CrossRefPubMedPubMedCentral
28.
Smeets E, Lynch AG, Prekovic S, Van den Broeck T, Moris L, Helsen C, et al. The role of TET-mediated DNA hydroxymethylation in prostate cancer. Mol Cell Endocrinol. 2018;462:41–55.CrossRefPubMed
29.
Huang Y, Tian C, Li Q, Xu Q. TET1 Knockdown Inhibits Porphyromonas gingivalis LPS/IFN-γ-Induced M1 Macrophage Polarization through the NF-κB Pathway in THP-1 Cells. Int J Mol Sci. 2019;20:2023.CrossRefPubMedPubMedCentral
30.
El-Kenawi A, Dominguez-Viqueira W, Liu M, Awasthi S, Abraham-Miranda J, Keske A, et al. Macrophage-derived cholesterol contributes to therapeutic resistance in prostate cancer. Cancer Res. 2021;81:5477–90.CrossRefPubMedPubMedCentral
31.
Escamilla J, Schokrpur S, Liu C, Priceman SJ, Moughon D, Jiang Z, et al. CSF1 receptor targeting in prostate cancer reverses macrophage-mediated resistance to androgen blockade therapy. Cancer Res. 2015;75:950–62.CrossRefPubMedPubMedCentral
32.
Li H, Yang P, Wang J, Zhang J, Ma Q, Jiang Y, et al. HLF regulates ferroptosis, development and chemoresistance of triple-negative breast cancer by activating tumor cell-macrophage crosstalk. J Hematol Oncol. 2022;15:2.CrossRefPubMedPubMedCentral
33.
Olson OC, Kim H, Quail DF, Foley EA, Joyce JA. Tumor-associated macrophages suppress the cytotoxic activity of antimitotic agents. Cell Rep. 2017;19:101–13.CrossRefPubMedPubMedCentral
34.
Liu L, Guo H, Song A, Huang J, Zhang Y, Jin S, et al. Progranulin inhibits LPS-induced macrophage M1 polarization via NF-кB and MAPK pathways. BMC Immunol. 2020;21:32.CrossRefPubMedPubMedCentral
35.
Liu J, Wei Y, Jia W, Can C, Wang R, Yang X, et al. Chenodeoxycholic acid suppresses AML progression through promoting lipid peroxidation via ROS/p38 MAPK/DGAT1 pathway and inhibiting M2 macrophage polarization. Redox Biol. 2022;56: 102452.CrossRefPubMedPubMedCentral
Metadata
Title
TET3 is expressed in prostate cancer tumor-associated macrophages and is associated with anti-androgen resistance
Authors
Qiu-ju Wei
Hai-qi Liang
Yao-wen Liang
Zu-xin Huang
Publication date
06-09-2024
Publisher
Springer International Publishing
Published in
Clinical and Translational Oncology
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-024-03708-w

2024 ESMO Congress

Add-on Ra223 could be a new first-line option in mCRPC

Adding radium-223 to first-line enzalutamide significantly improves the survival of patients with bone metastatic castration-resistant prostate cancer.

Read more

AI model can predict tumor mutations

No OS benefit of adding preoperative CRT in gastric cancer

T-DXd supported for breast cancer with brain metastases

» View more highlights on the ESMO 2024 hub page

Recent advances in the use of CAR T-cell therapies in relapsed/refractory diffuse large B-cell lymphoma and follicular lymphoma

  • Webinar | 01-10-2024 | 12:30 (CEST)

Live event concluded

In this webinar, Professor Martin Dreyling and an esteemed, international panel of CAR-T experts discuss the latest data on the safety, efficacy, and clinical impact of CAR T-cell therapies in the treatment of r/r DLBCL and r/r FL.

Please note, this webinar is not intended for healthcare professionals based in the US and UK.

Sponsored by: Novartis Pharma AG

Chaired by: Prof. Martin Dreyling
Developed by: Springer Healthcare
Get a reminder for the on-demand version
Image Credits