{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T09:07:10Z","timestamp":1785229630420,"version":"3.55.0"},"reference-count":56,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T00:00:00Z","timestamp":1748995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009945","name":"Merck","doi-asserted-by":"publisher","award":["10.13039\/100009945"],"award-info":[{"award-number":["10.13039\/100009945"]}],"id":[{"id":"10.13039\/100009945","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009945","name":"Merck","doi-asserted-by":"publisher","award":["P30CA016672"],"award-info":[{"award-number":["P30CA016672"]}],"id":[{"id":"10.13039\/100009945","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009945","name":"Merck","doi-asserted-by":"publisher","award":["P30CA071789"],"award-info":[{"award-number":["P30CA071789"]}],"id":[{"id":"10.13039\/100009945","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009945","name":"Merck","doi-asserted-by":"publisher","award":["P30GM114737"],"award-info":[{"award-number":["P30GM114737"]}],"id":[{"id":"10.13039\/100009945","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Characterized Cell Line Core Facility and Biostatistics Core","award":["10.13039\/100009945"],"award-info":[{"award-number":["10.13039\/100009945"]}]},{"name":"Characterized Cell Line Core Facility and Biostatistics Core","award":["P30CA016672"],"award-info":[{"award-number":["P30CA016672"]}]},{"name":"Characterized Cell Line Core Facility and Biostatistics Core","award":["P30CA071789"],"award-info":[{"award-number":["P30CA071789"]}]},{"name":"Characterized Cell Line Core Facility and Biostatistics Core","award":["P30GM114737"],"award-info":[{"award-number":["P30GM114737"]}]},{"name":"Shared Resources, Preclinical Core","award":["10.13039\/100009945"],"award-info":[{"award-number":["10.13039\/100009945"]}]},{"name":"Shared Resources, Preclinical Core","award":["P30CA016672"],"award-info":[{"award-number":["P30CA016672"]}]},{"name":"Shared Resources, Preclinical Core","award":["P30CA071789"],"award-info":[{"award-number":["P30CA071789"]}]},{"name":"Shared Resources, Preclinical Core","award":["P30GM114737"],"award-info":[{"award-number":["P30GM114737"]}]},{"name":"Centers of Biomedical Research Excellence program","award":["10.13039\/100009945"],"award-info":[{"award-number":["10.13039\/100009945"]}]},{"name":"Centers of Biomedical Research Excellence program","award":["P30CA016672"],"award-info":[{"award-number":["P30CA016672"]}]},{"name":"Centers of Biomedical Research Excellence program","award":["P30CA071789"],"award-info":[{"award-number":["P30CA071789"]}]},{"name":"Centers of Biomedical Research Excellence program","award":["P30GM114737"],"award-info":[{"award-number":["P30GM114737"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Triple-negative breast cancer (TNBC) and inflammatory breast cancer (IBC) are the most aggressive molecular subtypes of breast cancer. Poor clinical outcomes highlight the pressing need to discover novel targets for the effective treatment of these diseases. LMP7 (\u03b25i\/PSMB8), a proteolytic subunit of the immunoproteasome, is implicated in the pathogenesis of multiple myeloma, autoimmune and inflammatory diseases, and inflammation-related cancers. However, the role of LMP7 in TNBC and IBC remains poorly characterized. Here, we evaluated the function of LMP7 in TNBC and IBC using the selective LMP7 inhibitor M3258. In human TNBC patient samples, LMP7 expression correlated strongly with CD8+ T cell infiltration and activation markers. M3258 inhibited LMP7 activity, reduced viability, and induced apoptosis in TNBC\/IBC cell lines in vitro. In a novel immunocompetent in vivo model of TNBC\/IBC, M3258 reduced tumor growth and the tumor abundance of M2 macrophages. Additionally, M3258 activated tumor-infiltrating CD8+ T cells and suppressed the expression of specific inflammatory pathway gene signatures in immune cells. Co-culture with M2 macrophages enhanced the invasiveness of TNBC\/IBC cells, which was effectively suppressed by M3258 treatment. Our results demonstrate for the first time that LMP7 shapes the pro-tumorigenic microenvironment of TNBC\/IBC, in part by modulating the pathogenic role of M2 macrophages. These findings suggest that LMP7 may represent a novel target for therapeutic intervention in TNBC\/IBC.<\/jats:p>","DOI":"10.3390\/cancers17111887","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T03:58:52Z","timestamp":1749095932000},"page":"1887","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["LMP7-Specific Inhibitor M3258 Modulates the Tumor Microenvironment of Triple-Negative Breast Cancer and Inflammatory Breast Cancer"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0409-2294","authenticated-orcid":false,"given":"Xuemei","family":"Xie","sequence":"first","affiliation":[{"name":"Section of Translational Breast Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"Cancer Biology Program, University of Hawai\u02bbi Cancer Center, Honolulu, HI 96813, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jangsoon","family":"Lee","sequence":"additional","affiliation":[{"name":"Section of Translational Breast Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"Cancer Biology Program, University of Hawai\u02bbi Cancer Center, Honolulu, HI 96813, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganiraju C.","family":"Manyam","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0801-6632","authenticated-orcid":false,"given":"Troy","family":"Pearson","sequence":"additional","affiliation":[{"name":"Section of Translational Breast Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"Institute Associate Scientist IV Belfer Neurodegeneration Consort, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5775-5590","authenticated-orcid":false,"given":"Gina","family":"Walter-Bausch","sequence":"additional","affiliation":[{"name":"Merck Healthcare KGaA, 64293 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manja","family":"Friese-Hamim","sequence":"additional","affiliation":[{"name":"Merck KGaA, 64293 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Merck Healthcare KGaA, 64293 Darmstadt, Germany"},{"name":"Sanofi Deutschland, 60311 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4915-9966","authenticated-orcid":false,"given":"Julia","family":"Jabs","sequence":"additional","affiliation":[{"name":"Merck Healthcare KGaA, 64293 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela A.","family":"Manginelli","sequence":"additional","affiliation":[{"name":"Merck Healthcare KGaA, 64293 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Piske","sequence":"additional","affiliation":[{"name":"Merck Healthcare KGaA, 64293 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Mrowiec","sequence":"additional","affiliation":[{"name":"Merck Healthcare KGaA, 64293 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2978-2572","authenticated-orcid":false,"given":"Corinna M.","family":"Wolf","sequence":"additional","affiliation":[{"name":"Merck Healthcare KGaA, 64293 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharat S.","family":"Kuntal","sequence":"additional","affiliation":[{"name":"Cancer Biology Program, University of Hawai\u02bbi Cancer Center, Honolulu, HI 96813, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5711-2404","authenticated-orcid":false,"given":"Debu","family":"Tripathy","sequence":"additional","affiliation":[{"name":"Section of Translational Breast Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5362-486X","authenticated-orcid":false,"given":"Michael P.","family":"Sanderson","sequence":"additional","affiliation":[{"name":"Merck Healthcare KGaA, 64293 Darmstadt, Germany"},{"name":"Molecular Partners AG, 8952 Zurich-Schlieren, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0166-7275","authenticated-orcid":false,"given":"Naoto T.","family":"Ueno","sequence":"additional","affiliation":[{"name":"Section of Translational Breast Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"Cancer Biology Program, University of Hawai\u02bbi Cancer Center, Honolulu, HI 96813, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1084\/jem.193.11.1319","article-title":"Immunoproteasomes shape immunodominance hierarchies of antiviral CD8(+) T cells at the levels of T cell repertoire and presentation of viral antigens","volume":"193","author":"Chen","year":"2001","journal-title":"J. Exp. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1016\/j.cell.2013.01.037","article-title":"Immuno- and constitutive proteasomes do not differ in their abilities to degrade ubiquitinated proteins","volume":"152","author":"Nathan","year":"2013","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3033","DOI":"10.1111\/ajt.14435","article-title":"The immunoproteasome: An old player with a novel and emerging role in alloimmunity","volume":"17","author":"Eskandari","year":"2017","journal-title":"Am. J. Transplant."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/35056572","article-title":"Antigen processing by the proteasome","volume":"2","author":"Kloetzel","year":"2001","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1126\/science.8066463","article-title":"MHC class I expression in mice lacking the proteasome subunit LMP-7","volume":"265","author":"Fehling","year":"1994","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"101070","DOI":"10.1016\/j.gendis.2023.06.037","article-title":"The role of proteasomes in tumorigenesis","volume":"11","author":"Zhou","year":"2024","journal-title":"Genes Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nrclinonc.2016.206","article-title":"Proteasome inhibitors in cancer therapy","volume":"14","author":"Manasanch","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.2217\/fon.14.30","article-title":"Efficacy of therapy with bortezomib in solid tumors: A review based on 32 clinical trials","volume":"10","author":"Huang","year":"2014","journal-title":"Future Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1111\/jcmm.12279","article-title":"Proteasome inhibitors\u2014Molecular basis and current perspectives in multiple myeloma","volume":"18","author":"Kubiczkova","year":"2014","journal-title":"J. Cell Mol. Med."},{"key":"ref_10","first-page":"167","article-title":"Safety of proteasome inhibitors for treatment of multiple myeloma","volume":"16","author":"Schlafer","year":"2017","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kirk, C.J., Muchamuel, T., Wang, J., and Fan, R.A. (2021). Discovery and Early Clinical Development of Selective Immunoproteasome Inhibitors. Cells, 11.","DOI":"10.3390\/cells11010009"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"541984","DOI":"10.1155\/2015\/541984","article-title":"New Insights into the Function of the Immunoproteasome in Immune and Nonimmune Cells","volume":"2015","author":"Kimura","year":"2015","journal-title":"J. Immunol. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1158\/1535-7163.MCT-21-0005","article-title":"M3258 Is a Selective Inhibitor of the Immunoproteasome Subunit LMP7 (beta5i) Delivering Efficacy in Multiple Myeloma Models","volume":"20","author":"Sanderson","year":"2021","journal-title":"Mol. Cancer Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"10230","DOI":"10.1021\/acs.jmedchem.1c00604","article-title":"Structure-Based Optimization and Discovery of M3258, a Specific Inhibitor of the Immunoproteasome Subunit LMP7 (beta5i)","volume":"64","author":"Klein","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"115695","DOI":"10.1016\/j.taap.2021.115695","article-title":"Improved nonclinical safety profile of a novel, highly selective inhibitor of the immunoproteasome subunit LMP7 (M3258)","volume":"429","author":"Sloot","year":"2021","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"11127","DOI":"10.1021\/acs.jmedchem.8b01201","article-title":"Required Immunoproteasome Subunit Inhibition Profile for Anti-Inflammatory Efficacy and Clinical Candidate KZR-616 ((2 S,3 R)- N-((S)-3-(Cyclopent-1-en-1-yl)-1-((R)-2-methyloxiran-2-yl)-1-oxopropan-2-yl)-3-hydroxy-3-(4-methoxyphenyl)-2-((S)-2-(2-morpholinoacetamido)propanamido)propenamide)","volume":"61","author":"Johnson","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Muchamuel, T., Fan, R.A., Anderl, J.L., Bomba, D.J., Johnson, H.W.B., Lowe, E., Tuch, B.B., McMinn, D.L., Millare, B., and Kirk, C.J. (2023). Zetomipzomib (KZR-616) attenuates lupus in mice via modulation of innate and adaptive immune responses. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1043680"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"50873","DOI":"10.18632\/oncotarget.15141","article-title":"Inhibition and deficiency of the immunoproteasome subunit LMP7 suppress the development and progression of colorectal carcinoma in mice","volume":"8","author":"Koerner","year":"2017","journal-title":"Oncotarget"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1038\/s41416-022-02129-2","article-title":"Immunoproteasome inhibition prevents progression of castration-resistant prostate cancer","volume":"128","author":"Li","year":"2023","journal-title":"Br. J. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1002\/cncr.22836","article-title":"Differences in breast carcinoma characteristics in newly diagnosed African-American and Caucasian patients: A single-institution compilation compared with the National Cancer Institute\u2019s Surveillance, Epidemiology, and End Results database","volume":"110","author":"Morris","year":"2007","journal-title":"Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2792","DOI":"10.1016\/j.ejca.2009.06.027","article-title":"Triple-negative and HER2-overexpressing breast cancers exhibit an elevated risk and an earlier occurrence of cerebral metastases","volume":"45","author":"Heitz","year":"2009","journal-title":"Eur. J. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S73","DOI":"10.3816\/CBC.2009.s.008","article-title":"Biology, metastatic patterns, and treatment of patients with triple-negative breast cancer","volume":"9","author":"Anders","year":"2009","journal-title":"Clin. Breast Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5652","DOI":"10.1200\/JCO.2006.06.5664","article-title":"Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer","volume":"24","author":"Haffty","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4429","DOI":"10.1158\/1078-0432.CCR-06-3045","article-title":"Triple-negative breast cancer: Clinical features and patterns of recurrence","volume":"13","author":"Dent","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1634\/theoncologist.2012-0039","article-title":"Inflammatory breast cancer: What we know and what we need to learn","volume":"17","author":"Yamauchi","year":"2012","journal-title":"Oncologist"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1093\/jnci\/dji172","article-title":"Trends in inflammatory breast carcinoma incidence and survival: The surveillance, epidemiology, and end results program at the National Cancer Institute","volume":"97","author":"Hance","year":"2005","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1093\/annonc\/mdm480","article-title":"Inflammatory breast cancer in Tunisia in the era of multimodality therapy","volume":"19","author":"Labidi","year":"2008","journal-title":"Ann. Oncol."},{"key":"ref_28","first-page":"264","article-title":"Inflammatory breast cancer: What progress have we made?","volume":"25","author":"Dawood","year":"2011","journal-title":"Oncology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1634\/theoncologist.12-8-904","article-title":"Trends for inflammatory breast cancer: Is survival improving?","volume":"12","author":"Hennessy","year":"2007","journal-title":"Oncologist"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Geoffroy, K., Araripe Saraiva, B., Viens, M., Beland, D., and Bourgeois-Daigneault, M.C. (2023). Increased expression of the immunoproteasome subunits PSMB8 and PSMB9 by cancer cells correlate with better outcomes for triple-negative breast cancers. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-28940-2"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e201900562","DOI":"10.26508\/lsa.201900562","article-title":"Tradeoff between metabolic i-proteasome addiction and immune evasion in triple-negative breast cancer","volume":"3","author":"Adwal","year":"2020","journal-title":"Life Sci. Alliance"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1080\/07357900701506573","article-title":"A phase II study of single agent bortezomib in patients with metastatic breast cancer: A single institution experience","volume":"25","author":"Engel","year":"2007","journal-title":"Cancer Investig."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1093\/annonc\/mdj131","article-title":"Bortezomib (VELCADE) in metastatic breast cancer: Pharmacodynamics, biological effects, and prediction of clinical benefits","volume":"17","author":"Yang","year":"2006","journal-title":"Ann. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive Integration of Single-Cell Data","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nbt.4096","article-title":"Integrating single-cell transcriptomic data across different conditions, technologies, and species","volume":"36","author":"Butler","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"McInnes, L., and Healy, J. (2018). UMAP: Uniform Manifold Approximation and Projection for Dimension Reduction. arXiv.","DOI":"10.21105\/joss.00861"},{"key":"ref_37","unstructured":"Korotkevich, G., Sukhov, V., Budin, N., Shpak, B., Artyomov, M.N., and Sergushichev, A. (2019). Fast gene set enrichment analysis. bioRxiv."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B (Methodol.)"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Chen, D., Jin, C., Dong, X., Wen, J., Xia, E., Wang, Q., and Wang, O. (2021). Pan-cancer analysis of the prognostic and immunological role of PSMB8. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-99724-9"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1038\/s41467-020-14639-9","article-title":"Immunoproteasome expression is associated with better prognosis and response to checkpoint therapies in melanoma","volume":"11","author":"Kalaora","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.1182\/blood-2007-08-104950","article-title":"Molecular basis of bortezomib resistance: Proteasome subunit beta5 (PSMB5) gene mutation and overexpression of PSMB5 protein","volume":"112","author":"Oerlemans","year":"2008","journal-title":"Blood"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/s41416-020-01048-4","article-title":"Cytotoxic CD8(+) T cells in cancer and cancer immunotherapy","volume":"124","author":"Raskov","year":"2021","journal-title":"Br. J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1093\/intimm\/1.4.450","article-title":"Evidence for differential expression of CD45 isoforms by precursors for memory-dependent and independent cytotoxic responses: Human CD8 memory CTLp selectively express CD45RO (UCHL1)","volume":"1","author":"Merkenschlager","year":"1989","journal-title":"Int. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1111\/j.1365-2249.1991.tb05659.x","article-title":"Expression of CD45R0 (UCHL1) by CD4+ and CD8+ T cells as a sign of in vivo activation in infectious mononucleosis","volume":"83","author":"Miyawaki","year":"1991","journal-title":"Clin. Exp. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Chen, Y., Song, Y., Du, W., Gong, L., Chang, H., and Zou, Z. (2019). Tumor-associated macrophages: An accomplice in solid tumor progression. J. Biomed. Sci., 26.","DOI":"10.1186\/s12929-019-0568-z"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1146\/annurev-pharmtox-010919-023603","article-title":"Proteasome Inhibitor Drugs","volume":"60","author":"Fricker","year":"2020","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e503","DOI":"10.1038\/bcj.2016.112","article-title":"The role of the proteasome in AML","volume":"6","author":"Csizmar","year":"2016","journal-title":"Blood Cancer J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/978-3-030-40204-4_10","article-title":"Lessons Learned from Proteasome Inhibitors, the Paradigm for Targeting Protein Homeostasis in Cancer","volume":"1243","author":"Kambhampati","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4143\/crt.2017.500","article-title":"Expression of Immunoproteasome Subunit LMP7 in Breast Cancer and Its Association with Immune-Related Markers","volume":"51","author":"Lee","year":"2019","journal-title":"Cancer Res. Treat."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Roeten, M.S., van Meerloo, J., Kwidama, Z.J., Ter Huizen, G., Segerink, W.H., Zweegman, S., Kaspers, G.J.L., Jansen, G., and Cloos, J. (2021). Pre-Clinical Evaluation of the Proteasome Inhibitor Ixazomib against Bortezomib-Resistant Leukemia Cells and Primary Acute Leukemia Cells. Cells, 10.","DOI":"10.3390\/cells10030665"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"82482","DOI":"10.18632\/oncotarget.12694","article-title":"Mesenchymal stem cells and macrophages interact through IL-6 to promote inflammatory breast cancer in pre-clinical models","volume":"7","author":"Wolfe","year":"2016","journal-title":"Oncotarget"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1093\/jnci\/djab128","article-title":"Identification of the JNK-Active Triple-Negative Breast Cancer Cluster Associated With an Immunosuppressive Tumor Microenvironment","volume":"114","author":"Semba","year":"2022","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1080\/14728222.2022.2077188","article-title":"Emerging drug targets for triple-negative breast cancer: A guided tour of the preclinical landscape","volume":"26","author":"Xie","year":"2022","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Du, S.H., Xiang, Y.J., Liu, L., Nie, M., Hou, Y., Wang, L., Li, B.B., Xu, M., Teng, Q.L., and Peng, J. (2020). Co-Inhibition of the Immunoproteasome Subunits LMP2 and LMP7 Ameliorates Immune Thrombocytopenia. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.603278"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e46512","DOI":"10.15252\/embr.201846512","article-title":"Co-inhibition of immunoproteasome subunits LMP2 and LMP7 is required to block autoimmunity","volume":"19","author":"Basler","year":"2018","journal-title":"EMBO Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/s41392-021-00506-6","article-title":"Targeting macrophages in cancer immunotherapy","volume":"6","author":"Duan","year":"2021","journal-title":"Signal Transduct. Target. Ther."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/11\/1887\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:46:47Z","timestamp":1760032007000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/11\/1887"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,4]]},"references-count":56,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["cancers17111887"],"URL":"https:\/\/doi.org\/10.3390\/cancers17111887","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,4]]}}}