{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T23:05:13Z","timestamp":1792537513735,"version":"4.5.0"},"reference-count":129,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Multiple myeloma (MM) is a virtually incurable plasma cell malignancy characterized by malignant cells that expand within the tumor-permissive bone marrow (BM) microenvironment. Novel strategies are urgently needed to improve the outcomes of patients with difficult-to-treat and therapy-refractory disease. The ability to genetically manipulate T-cells and the introduction of adoptive cellular therapies (ACTs) has improved the treatment of relapsed and\/or refractory (RR)MM. Emerging evidence supports the efficacy of ACTs as early lines of cancer treatment, potentially even as an alternative to autologous hematopoietic stem cell transplantation. Chimeric antigen receptor (CAR) T-cell therapies based upon genetically engineered patient-derived T-cells are utilized in routine clinical practice, however severe toxicities, therapeutic resistance, exorbitant costs, a cumbersome manufacturing process and production logistics limits their broader application. Tumor-infiltrating lymphocytes (TILs) can also mediate tumor regression and lead to durable responses, but wider efficacy is restricted by limited accessibility, reduced proliferative capacity and low effector function. In this context, autologous T-cells engineered to express T-cell receptors (TCRs) represent an intriguing option to improve MM treatment. Immunoproteasomes represent an essential cornerstone of adaptive immunity and are required for the efficient processing of antigenic peptides presented by MHC class I (MHC-I) molecules to cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-lymphocytes (CTLs). Recent studies have demonstrated that immunoproteasome activation increases the presentation of tumor-specific neo-antigens, thereby offering a potential strategy to improve the antimyeloma effects of T-cell-mediated immunotherapies. Here, we discuss advantages and strategies that support the administration of TCR-engineered T-cells for the treatment of MM. This review focuses on the role of immunoproteasome dependent antigen processing in shaping the myeloma immunopeptidome and enabling TCR-based immunotherapy. We discuss how modulation of neoantigen presentation may inform the design of TCR-engineered T cells and related immunotherapeutic strategies for MM.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1755096","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T05:33:17Z","timestamp":1774935197000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Engineering TCR-directed T-cells for the treatment of multiple myeloma"],"prefix":"10.3389","volume":"17","author":[{"given":"Nida","family":"Mubin","sequence":"first","affiliation":[{"name":"Division of Hematology & Oncology, Case Western Reserve University","place":["Cleveland, OH, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Ignatz-Hoover","sequence":"additional","affiliation":[{"name":"Division of Hematology & Oncology, Case Western Reserve University","place":["Cleveland, OH, United States"]},{"name":"Adult Hematologic Malignancies & Stem Cell Transplant Section, Seidman Cancer Center, University Hospitals Cleveland Medical Center","place":["Cleveland, OH, United States"]},{"name":"Case Comprehensive Cancer Center, Case Western Reserve University","place":["Cleveland, OH, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Driscoll","sequence":"additional","affiliation":[{"name":"Division of Hematology & Oncology, Case Western Reserve University","place":["Cleveland, OH, United States"]},{"name":"Adult Hematologic Malignancies & Stem Cell Transplant Section, Seidman Cancer Center, University Hospitals Cleveland Medical Center","place":["Cleveland, OH, United States"]},{"name":"Case Comprehensive Cancer Center, Case Western Reserve University","place":["Cleveland, OH, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1001\/jamaoncol.2016.3160","article-title":"Association of minimal residual disease with superior survival outcomes in patients with multiple myeloma: A meta-analysis","volume":"3","author":"Munshi","year":"2017","journal-title":"JAMA Oncol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e1406","DOI":"10.1634\/theoncologist.2020-0141","article-title":"Multiple myeloma incidence and mortality around the globe; interrelations between health access and quality, economic resources, and patient empowerment","volume":"25","author":"Ludwig","year":"2020","journal-title":"Oncologist"},{"key":"B3","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1016\/S0140-6736(21)00135-5","article-title":"Multiple myeloma","volume":"397","author":"van de Donk","year":"2021","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21708","article-title":"Cancer statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J Clin"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1001\/jamaoncol.2018.2128","article-title":"Global burden of multiple myeloma: A systematic analysis for the global burden of disease study 2016","volume":"4","author":"Cowan","year":"2018","journal-title":"JAMA Oncol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-022-01234-2","article-title":"Deciphering mechanisms of immune escape to inform immunotherapeutic strategies in multiple myeloma","volume":"15","author":"Swamydas","year":"2022","journal-title":"J Hematol Oncol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1002\/ajh.25791","article-title":"Multiple myeloma: 2020 update on diagnosis, risk-stratification and management","volume":"95","author":"Rajkumar","year":"2020","journal-title":"Am J Hematol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1001\/jama.2022.0003","article-title":"Diagnosis and management of multiple myeloma: A review","volume":"327","author":"Cowan","year":"2022","journal-title":"JAMA"},{"key":"B9","doi-asserted-by":"publisher","first-page":"647","DOI":"10.20517\/cdr.2022.23","article-title":"Therapeutics to harness the immune microenvironment in multiple myeloma","volume":"5","author":"Ignatz-Hoover","year":"2022","journal-title":"Cancer Drug Resist"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13061285","article-title":"Multiple myeloma: heterogeneous in every way","volume":"13","author":"Schavgoulidze","year":"2021","journal-title":"Cancers"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28266-z","article-title":"Deciphering spatial genomic heterogeneity at a single cell resolution in multiple myeloma","volume":"13","author":"Merz","year":"2022","journal-title":"Nat Commun"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-47906-y","article-title":"A population-based study on incidence trends of myeloma in the United States over 2000\u20132020","volume":"13","author":"Mousavi","year":"2023","journal-title":"Sci Rep"},{"key":"B13","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1111\/ejh.13083","article-title":"Rapidly changing myeloma epidemiology in the general population: Increased incidence, older patients, and longer survival","volume":"101","author":"Turesson","year":"2018","journal-title":"Eur J Haematol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"3147","DOI":"10.1182\/blood-2012-07-443606","article-title":"Uncovering the biology of multiple myeloma among African Americans: a comprehensive genomics approach","volume":"121","author":"Baker","year":"2013","journal-title":"Blood"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-019-0177-9","article-title":"Molecular underpinnings of clinical disparity patterns in African American vs. Caucasian American multiple myeloma patients","volume":"9","author":"Kazandjian","year":"2019","journal-title":"Blood Cancer J"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1691","DOI":"10.1038\/leu.2009.134","article-title":"Patterns of monoclonal gammopathy of undetermined significance and multiple myeloma in various ethnic\/racial groups: support for genetic factors in pathogenesis","volume":"23","author":"Landgren","year":"2009","journal-title":"Leukemia"},{"key":"B17","doi-asserted-by":"publisher","first-page":"2615","DOI":"10.1182\/blood.2019000406","article-title":"With equal access, African American patients have superior survival compared to white patients with multiple myeloma: a VA study","volume":"133","author":"Fillmore","year":"2019","journal-title":"Blood"},{"key":"B18","doi-asserted-by":"publisher","first-page":"166","DOI":"10.46883\/2023.25920993","article-title":"Emerging strategies to manage relapsed and\/or refractory multiple myeloma","volume":"37","author":"Driscoll","year":"2023","journal-title":"Oncol (Williston Park)"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-022-00757-8","article-title":"Second- and third-line treatment strategies in multiple myeloma: a referral-center experience","volume":"12","author":"Goldman-Mazur","year":"2022","journal-title":"Blood Cancer J"},{"key":"B20","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1001\/jamainternmed.2024.8124","article-title":"Diagnosis and management of monoclonal gammopathy of undetermined significance: A review","volume":"185","author":"Liu","year":"2025","journal-title":"JAMA Intern Med"},{"key":"B21","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1182\/blood.2024025415","article-title":"Comparison of progression risk of monoclonal gammopathy of undetermined significance by method of detection","volume":"145","author":"Visram","year":"2025","journal-title":"Blood"},{"key":"B22","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1200\/JCO.2017.76.5032","article-title":"Improvement in overall survival with carfilzomib, lenalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma","volume":"36","author":"Siegel","year":"2018","journal-title":"J Clin Oncol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1411","DOI":"10.1002\/ajh.27314","article-title":"Comparative efficacy of carfilzomib, lenalidomide, and dexamethasone (KRd) versus bortezomib, lenalidomide, and dexamethasone (VRd) in newly-diagnosed multiple myeloma: A systematic review and meta-analysis","volume":"99","author":"Costa","year":"2024","journal-title":"Am J Hematol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1182\/blood.2024027065","article-title":"Is it time to screen for multiple myeloma","volume":"145","author":"Ghobrial","year":"2025","journal-title":"Blood"},{"key":"B25","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1016\/S0140-6736(21)00933-8","article-title":"Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b\/2 open-label study","volume":"398","author":"Berdeja","year":"2021","journal-title":"Lancet"},{"key":"B26","doi-asserted-by":"publisher","first-page":"2739","DOI":"10.1200\/JCO-24-01893","article-title":"International Myeloma Society\/International Myeloma Working Group consensus recommendations on the definition of high-risk multiple myeloma","volume":"43","author":"Avet-Loiseau","year":"2025","journal-title":"J Clin Oncol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1007\/s10555-017-9698-5","article-title":"Emerging small molecule approaches to enhance the antimyeloma benefit of proteasome inhibitors","volume":"36","author":"Driscoll","year":"2017","journal-title":"Cancer Metastasis Rev"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1141851","article-title":"Shutting off the fuel supply to target metabolic vulnerabilities in multiple myeloma","volume":"13","author":"Rana","year":"2023","journal-title":"Front Oncol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.1059715","article-title":"Targeting TGF-\u03b2 signaling in the multiple myeloma microenvironment: Steering CARs and T cells in the right direction","volume":"10","author":"Rana","year":"2022","journal-title":"Front Cell Dev Biol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2025.1578529","article-title":"Revolutions at the frontline of multiple myeloma treatment: lessons and challenges to finding a cure","volume":"20","author":"Kort","year":"2025","journal-title":"Front Oncol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3390\/cells9030601","article-title":"Immunotherapy in multiple myeloma","volume":"9","author":"Soekojo","year":"2020","journal-title":"Cells"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.m3176","article-title":"Emerging immunotherapies in multiple myeloma","volume":"370","author":"Shah","year":"2020","journal-title":"BMJ"},{"key":"B33","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1038\/nature22395","article-title":"Therapeutic T cell engineering","volume":"545","author":"Sadelain","year":"2017","journal-title":"Nature"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1688","DOI":"10.1182\/blood-2016-04-711903","article-title":"T cells expressing an anti\u2013B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma","volume":"128","author":"Ali","year":"2016","journal-title":"Blood"},{"key":"B35","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1158\/2159-8290.CD-12-0548","article-title":"The basic principles of chimeric antigen receptor design","volume":"3","author":"Sadelain","year":"2013","journal-title":"Cancer Discov"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.957157","article-title":"Road testing new CAR design strategies in multiple myeloma","volume":"13","author":"Rana","year":"2022","journal-title":"Front Immunol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1038\/s41375-020-0734-z","article-title":"B-cell maturation antigen (BCMA) in multiple myeloma: rationale for targeting and current therapeutic approaches","volume":"34","author":"Shah","year":"2020","journal-title":"Leukemia"},{"key":"B38","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1182\/blood.2025030559","article-title":"The fully human anti-GPRC5D CAR T-cell therapy RD118 induces durable remissions in relapsed\/refractory multiple myeloma","volume":"147","author":"Pan","year":"2026","journal-title":"Blood"},{"key":"B39","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1182\/blood.2022015526","article-title":"Efficacy and safety of cilta-cel in patients with progressive multiple myeloma after exposure to other BCMA-targeting agents","volume":"141","author":"Cohen","year":"2023","journal-title":"Blood"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1056\/NEJMoa2213614","article-title":"Ide-cel or standard regimens in relapsed and refractory multiple myeloma","volume":"388","author":"Rodriguez-Otero","year":"2023","journal-title":"N Engl J Med"},{"key":"B41","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1056\/NEJMoa2024850","article-title":"Idecabtagene vicleucel in relapsed and refractory multiple myeloma","volume":"384","author":"Munshi","year":"2021","journal-title":"N Engl J Med"},{"key":"B42","doi-asserted-by":"publisher","first-page":"169","DOI":"10.20517\/cdr.2022.138","article-title":"Anti-BCMA novel therapies for multiple myeloma","volume":"6","author":"Sammartano","year":"2023","journal-title":"Cancer Drug Resist"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-025-01675-5","article-title":"BCMA-targeted therapies for multiple myeloma: latest updates from 2024 ASH annual meeting","volume":"18","author":"Zheng","year":"2025","journal-title":"J Hematol Oncol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"2295","DOI":"10.1038\/s41591-023-02491-5","article-title":"Mechanisms of antigen escape from BCMA- or GPRC5D-targeted immunotherapies in multiple myeloma","volume":"29","author":"Lee","year":"2023","journal-title":"Nat Med"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1534","DOI":"10.1038\/s43018-023-00637-5","article-title":"Myeloma evades T cell-engaging therapies","volume":"4","author":"Paiva","year":"2023","journal-title":"Nat Cancer"},{"key":"B46","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1182\/blood.2023023557","article-title":"Antigen escape as a shared mechanism of resistance to BCMA-directed therapies in multiple myeloma","volume":"144","author":"Firestone","year":"2024","journal-title":"Blood"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-025-01410-w","article-title":"Clinical experience with cranial nerve palsy in patients infused with ciltacabtagene autoleucel for the treatment of relapsed\/refractory MM in CARTITUDE-1, -2, and -4","volume":"15","author":"Rodr\u00edguez-Otero","year":"2025","journal-title":"Blood Cancer J"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1182\/blood.2023020571","article-title":"Neurologic toxicities following adoptive immunotherapy with BCMA-directed CAR T cells","volume":"142","author":"Karschnia","year":"2023","journal-title":"Blood"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1182\/blood.2023021860","article-title":"BCMA-CAR T-cell treatment\u2013associated parkinsonism","volume":"142","author":"Gust","year":"2023","journal-title":"Blood"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1007\/s00018-011-0657-y","article-title":"The role of the proteasome in the generation of MHC class I ligands and immune responses","volume":"68","author":"Sijts","year":"2011","journal-title":"Cell Mol Life Sci"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2022.215840","article-title":"Neoantigen-targeted TCR-T cell therapy for solid tumors: How far from clinical application","volume":"546","author":"Xu","year":"2022","journal-title":"Cancer Lett"},{"key":"B52","doi-asserted-by":"publisher","first-page":"244","DOI":"10.3324\/haematol.2024.286124","article-title":"A phase I study of MAGE-A1-targeted T1367 T-cell receptor-based cell therapy in patients with advanced multiple myeloma","volume":"110","author":"Kr\u00fcger","year":"2025","journal-title":"Haematologica"},{"key":"B53","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1038\/nrg3199","article-title":"Endogenous viruses: insights into viral evolution and impact on host biology","volume":"13","author":"Feschotte","year":"2012","journal-title":"Nat Rev Genet"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19464-8","article-title":"Human endogenous retroviruses form a reservoir of T cell targets in hematological cancers","volume":"11","author":"Saini","year":"2020","journal-title":"Nat Commun"},{"key":"B55","doi-asserted-by":"publisher","first-page":"2113","DOI":"10.1056\/NEJMoa2210233","article-title":"Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma","volume":"387","author":"Rohaan","year":"2022","journal-title":"N Engl J Med"},{"key":"B56","doi-asserted-by":"publisher","first-page":"997","DOI":"10.2147\/ITT.S534784","article-title":"T cells dysfunction in multiple myeloma","volume":"14","author":"Cai","year":"2025","journal-title":"Immunotargets Ther"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2014.07.028","article-title":"The interplay between autophagy and the ubiquitin-proteasome system in cardiac proteotoxicity","volume":"1852","author":"Wang","year":"2015","journal-title":"Biochim Biophys Acta"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.05.081","article-title":"The ubiquitin-proteasome pathway and its role in cancer","volume":"23","author":"Mani","year":"2005","journal-title":"J Clin Oncol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/637629","article-title":"Genetics of proteasome diseases","volume":"2013","author":"Gomes","year":"2013","journal-title":"Scientifica (Cairo)"},{"key":"B60","doi-asserted-by":"publisher","first-page":"4789","DOI":"10.1016\/S0021-9258(19)34041-4","article-title":"The proteasome (multicatalytic protease) is a component of the 1500-kDa proteolytic complex which degrades ubiquitin-conjugated proteins","volume":"265","author":"Driscoll","year":"1990","journal-title":"J Biol Chem"},{"key":"B61","doi-asserted-by":"publisher","first-page":"12412","DOI":"10.1016\/S0021-9258(18)37771-8","article-title":"A multicomponent system that degrades proteins conjugated to ubiquitin. Resolution of factors and evidence for ATP-dependent complex formation","volume":"263","author":"Ganoth","year":"1988","journal-title":"J Biol Chem"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52513-0","article-title":"Structural basis of human 20S proteasome biogenesis","volume":"15","author":"Zhang","year":"2024","journal-title":"Nat Commun"},{"key":"B63","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1146\/annurev.pharmtox.051208.165340","article-title":"Targeting proteins for destruction by the ubiquitin system: implications for human pathobiology","volume":"49","author":"Schwartz","year":"2009","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"B64","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1146\/annurev.biochem.78.081507.101607","article-title":"Recognition and processing of ubiquitin-protein conjugates by the proteasome","volume":"78","author":"Finley","year":"2009","journal-title":"Annu Rev Biochem"},{"key":"B65","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/j.molcel.2024.12.015","article-title":"Ubiquitin-A structural perspective","volume":"85","author":"Agrata","year":"2025","journal-title":"Mol Cell"},{"key":"B66","first-page":"197","article-title":"The role of the proteasome in cellular protein degradation","volume":"9","author":"Driscoll","year":"1994","journal-title":"Histol Histopathol"},{"key":"B67","doi-asserted-by":"publisher","first-page":"4986","DOI":"10.1073\/pnas.89.11.4986","article-title":"An ATP-stabilized inhibitor of the proteasome is a component of the 1500-kDa ubiquitin conjugate-degrading complex","volume":"89","author":"Driscoll","year":"1992","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.12279","article-title":"Proteasome inhibitors - molecular basis and current perspectives in multiple myeloma","volume":"18","author":"Kubiczkova","year":"2014","journal-title":"J Cell Mol Med"},{"key":"B69","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1006\/abbi.2000.2036","article-title":"Catalytic activities of the 20 S proteasome, a multicatalytic proteinase complex","volume":"383","author":"Orlowski","year":"2000","journal-title":"Arch Biochem Biophys"},{"key":"B70","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1042\/EB0410031","article-title":"Proteasomes","volume":"41","author":"Dahlmann","year":"2005","journal-title":"Essays Biochem"},{"key":"B71","doi-asserted-by":"publisher","first-page":"10289","DOI":"10.1021\/bi00497a001","article-title":"The multicatalytic proteinase complex, a major extralysosomal proteolytic system","volume":"29","author":"Orlowski","year":"1990","journal-title":"Biochemistry"},{"key":"B72","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1111\/j.1471-4159.1983.tb08056.x","article-title":"Evidence that pituitary cation-sensitive neutral endopeptidase is a multicatalytic protease complex","volume":"40","author":"Wilk","year":"1983","journal-title":"J Neurochem"},{"key":"B73","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1073\/pnas.86.3.787","article-title":"Skeletal muscle proteasome can degrade proteins in an ATP-dependent process that does not require ubiquitin","volume":"86","author":"Driscoll","year":"1989","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B74","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1038\/365262a0","article-title":"MHC-linked LMP gene-products specifically alter peptidase activities of the proteasome","volume":"365","author":"Driscoll","year":"1993","journal-title":"Nature"},{"key":"B75","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1016\/0092-8674(92)90024-7","article-title":"A controlled breakdown - antigen processing and the turnover of viral-proteins","volume":"68","author":"Driscoll","year":"1992","journal-title":"Cell"},{"key":"B76","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/353355a0","article-title":"Structural and serological similarity of MHC-linked lmp and proteasome (Multicatalytic proteinase) complexes","volume":"353","author":"Brown","year":"1991","journal-title":"Nature"},{"key":"B77","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.coi.2003.11.004","article-title":"Proteasome and peptidase function in MHC-class-I-mediated antigen presentation","volume":"16","author":"Kloetzel","year":"2004","journal-title":"Curr Opin Immunol"},{"key":"B78","doi-asserted-by":"publisher","first-page":"3439","DOI":"10.1002\/eji.201040620","article-title":"Immunoproteasomes are essential for survival and expansion of T cells in virus-infected mice","volume":"40","author":"Moebius","year":"2010","journal-title":"Eur J Immunol"},{"key":"B79","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1093\/oxfordjournals.jbchem.a124327","article-title":"Interferon-gamma induces different subunit organizations and functional diversity of proteasomes","volume":"115","author":"Aki","year":"1994","journal-title":"J Biochem"},{"key":"B80","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/0014-5793(94)80612-8","article-title":"Replacement of proteasome subunits X and Y by LMP7 and LMP2 induced by interferon-gamma for acquirement of the functional diversity responsible for antigen processing","volume":"343","author":"Akiyama","year":"1994","journal-title":"FEBS Lett"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.636568","article-title":"Cancer immune evasion through loss of MHC class I antigen presentation","volume":"12","author":"DhatChinamoorthy","year":"2021","journal-title":"Front Immunol"},{"key":"B82","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1038\/s41577-022-00707-2","article-title":"A guide to antigen processing and presentation","volume":"22","author":"Pishesha","year":"2022","journal-title":"Nat Rev Immunol"},{"key":"B83","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1038\/nri3084","article-title":"Towards a systems understanding of MHC class I and MHC class II antigen presentation","volume":"11","author":"Neefjes","year":"2011","journal-title":"Nat Rev Immunol"},{"key":"B84","doi-asserted-by":"publisher","first-page":"994","DOI":"10.3390\/biom4040994","article-title":"Proteasome subtypes and regulators in the processing of antigenic peptides presented by class I molecules of the major histocompatibility complex","volume":"4","author":"Vigneron","year":"2014","journal-title":"Biomolecules"},{"key":"B85","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1042\/BJ20100878","article-title":"The immunoproteasome, the 20S proteasome and the PA28\u03b1\u03b2 proteasome regulator are oxidative-stress-adaptive proteolytic complexes","volume":"432","author":"Pickering","year":"2010","journal-title":"Biochem J"},{"key":"B86","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1023\/a:1006897801858","article-title":"Structural and functional properties of proteasome activator PA28","volume":"24","author":"Kuehn","year":"1997","journal-title":"Mol Biol Rep"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.3390\/biom11020228","article-title":"PA28\u03b3: new insights on an ancient proteasome activator","volume":"11","author":"Cascio","year":"2021","journal-title":"Biomolecules"},{"key":"B88","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/s12276-024-01385-x","article-title":"Activators of the 26S proteasome when protein degradation increases","volume":"57","author":"Lee","year":"2025","journal-title":"Exp Mol Med"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19934-z","article-title":"Conformational maps of human 20S proteasomes reveal PA28- and immuno-dependent inter-ring crosstalks","volume":"11","author":"Lesne","year":"2020","journal-title":"Nat Commun"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.AM2023-6235","article-title":"Discovery of novel HDAC6 inhibitors that enhance proteasomal activity to boost antigen presentation and trigger anti-myeloma T-cell immunity","volume":"83","author":"Rana","year":"2022","journal-title":"Cancer Res"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15235632","article-title":"Targeting proteasomes and the MHC class I antigen presentation machinery to treat cancer, infections and age-related diseases","volume":"15","author":"Rana","year":"2023","journal-title":"Cancers"},{"key":"B92","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.1158\/2767-9764.CRC-23-0528","article-title":"HDAC6 inhibition releases HR23B to activate proteasomes, expand the tumor immunopeptidome and amplify T-cell antimyeloma activity","volume":"4","author":"Rana","year":"2024","journal-title":"Cancer Res Commun"},{"key":"B93","first-page":"S505","article-title":"Novel proteasome activators that enhance MHC class I antigen presentation and trigger anti-Myeloma T-Cell immunity","volume":"23","author":"Rana","year":"2023","journal-title":"Clin Lymphoma Myeloma Leuk"},{"key":"B94","doi-asserted-by":"publisher","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":"B95","doi-asserted-by":"publisher","first-page":"6469","DOI":"10.1021\/acs.jmedchem.9b00101","article-title":"Proteasome activation as a new therapeutic approach to target proteotoxic disorders","volume":"62","author":"Njomen","year":"2019","journal-title":"J Med Chem"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24122341","article-title":"Methods to discover and evaluate proteasome small molecule stimulators","volume":"24","author":"Coleman","year":"2019","journal-title":"Molecules"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-025-01563-w","article-title":"Generation of T cells with reduced off-target cross-reactivities by engineering co-signalling receptors","author":"Cabezas-Caballero","year":"2026","journal-title":"Nat Biomed Eng"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2025-2176","article-title":"Synthetic lethal targeting of PSMC2-dependent p97-adapted proteasome complexes that confer chemo-resistance in multiple myeloma","volume":"146","author":"Driscoll","year":"2025","journal-title":"Blood"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2024-211260","article-title":"PSMC2 overexpression promotes synthetic lethality sensitizing multiple myeloma cells to p97 inhibition","volume":"144","author":"Ignatz-Hoover","year":"2024","journal-title":"Blood"},{"key":"B100","doi-asserted-by":"publisher","first-page":"E1555","DOI":"10.1073\/pnas.1521812113","article-title":"Immunoproteasome deficiency is a feature of non-small cell lung cancer with a mesenchymal phenotype and is associated with a poor outcome","volume":"113","author":"Tripathi","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B101","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1038\/nm.1978","article-title":"A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis","volume":"15","author":"Muchamuel","year":"2009","journal-title":"Nat Med"},{"key":"B102","doi-asserted-by":"publisher","first-page":"3903","DOI":"10.1016\/j.cell.2023.07.016","article-title":"A membrane-associated MHC-I inhibitory axis for cancer immune evasion","volume":"186","author":"Chen","year":"2023","journal-title":"Cell"},{"key":"B103","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1038\/nature10755","article-title":"Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting","volume":"482","author":"Matsushita","year":"2012","journal-title":"Nature"},{"key":"B104","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1158\/0008-5472.CAN-11-3722","article-title":"Exploiting the mutanome for tumor vaccination","volume":"72","author":"Castle","year":"2012","journal-title":"Cancer Res"},{"key":"B105","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1126\/science.aaa1348","article-title":"Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer","volume":"348","author":"Rizvi","year":"2015","journal-title":"Science"},{"key":"B106","doi-asserted-by":"publisher","first-page":"1726","DOI":"10.1038\/s41590-025-02252-1","article-title":"TCR-engineered T cells targeting a shared \u03b2-catenin mutation eradicate solid tumors","volume":"26","author":"Eggeb\u00f8","year":"2025","journal-title":"Nat Immunol"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1360281","article-title":"IMPROVE: a feature model to predict neoepitope immunogenicity through broad-scale validation of T-cell recognition","volume":"15","author":"Borch","year":"2024","journal-title":"Front Immunol"},{"key":"B108","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1158\/2159-8290.CD-18-1494","article-title":"Unique Neoantigens Arise from Somatic Mutations in Patients with Gastrointestinal Cancers","volume":"9","author":"Parkhurst","year":"2019","journal-title":"Cancer Discov"},{"key":"B109","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1038\/s43018-021-00210-y","article-title":"Targeting public neoantigens for cancer immunotherapy","volume":"2","author":"Pearlman","year":"2021","journal-title":"Nat Cancer"},{"key":"B110","doi-asserted-by":"publisher","first-page":"6178","DOI":"10.1182\/bloodadvances.2023010410","article-title":"Combining BCMA-targeting CAR T cells with TCR-engineered T-cell therapy to prevent immune escape of multiple myeloma","volume":"7","author":"Wachsmann","year":"2023","journal-title":"Blood Adv"},{"key":"B111","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1182\/blood-2015-04-640532","article-title":"The antigenic landscape of multiple myeloma: mass spectrometry (re)defines targets for T-cell\u2013based immunotherapy","volume":"126","author":"Walz","year":"2015","journal-title":"Blood"},{"key":"B112","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1182\/blood-2015-07-657130","article-title":"Expanding the peptidome for immunotherapy","volume":"126","author":"Neefjes","year":"2015","journal-title":"Blood"},{"key":"B113","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1038\/s41577-018-0007-5","article-title":"Understanding the drivers of MHC restriction of T cell receptors","volume":"18","author":"La Gruta","year":"2018","journal-title":"Nat Rev Immunol"},{"key":"B114","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1158\/2159-8290.CD-20-1575","article-title":"Exploiting tumor neoantigens to target cancer evolution: current challenges and promising therapeutic approaches","volume":"11","author":"Gupta","year":"2021","journal-title":"Cancer Discov"},{"key":"B115","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1038\/s41587-021-01038-8","article-title":"Identification of tumor antigens with immunopeptidomics","volume":"40","author":"Chong","year":"2022","journal-title":"Nat Biotechnol"},{"key":"B116","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1038\/s41586-022-04839-2","article-title":"Deciphering the immunopeptidome in vivo reveals new tumour antigens","volume":"607","author":"Jaeger","year":"2022","journal-title":"Nature"},{"key":"B117","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1038\/nm.3910","article-title":"NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma","volume":"21","author":"Rapoport","year":"2015","journal-title":"Nat Med"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-023-00713-y","article-title":"A systematic safety pipeline for selection of T-cell receptors to enter clinical use","volume":"8","author":"Foldvari","year":"2023","journal-title":"NPJ Vaccines"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-021-02076-5","article-title":"CRISPR\/Cas9 revitalizes adoptive T-cell therapy for cancer immunotherapy","volume":"40","author":"Ghaffari","year":"2021","journal-title":"J Exp Clin Cancer Res"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32521-8","article-title":"Lactate increases stemness of CD8\u2009+\u2009T cells to augment anti-tumor immunity","volume":"13","author":"Feng","year":"2022","journal-title":"Nat Commun"},{"key":"B121","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1016\/j.celrep.2018.01.040","article-title":"Early TCR Signaling Induces Rapid Aerobic Glycolysis Enabling Distinct Acute T Cell Effector Functions","volume":"22","author":"Menk","year":"2018","journal-title":"Cell Rep"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1002\/hem3.70182","article-title":"Harnessing the immunotherapeutic potentials of gamma delta T cells against hematological Malignancies","volume":"9","author":"Agbuduwe","year":"2025","journal-title":"Hemasphere"},{"key":"B123","doi-asserted-by":"publisher","first-page":"2931","DOI":"10.1182\/blood.2024027496","article-title":"Reprogramming glutamine metabolism enhances BCMA-CAR T-cell fitness and therapeutic efficacy in multiple myeloma","volume":"146","author":"Navarro","year":"2025","journal-title":"Blood"},{"key":"B124","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.ccell.2015.08.009","article-title":"Engineering anti-myeloma responses using affinity-enhanced TCR-engineered T cells","volume":"28","author":"San Miguel","year":"2015","journal-title":"Cancer Cell"},{"key":"B125","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1182\/bloodadvances.2020001792","article-title":"BiTEs better than CAR T cells","volume":"5","author":"Subklewe","year":"2021","journal-title":"Blood Adv"},{"key":"B126","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1111\/imr.13233","article-title":"Challenges and solutions for therapeutic TCR-based agents","volume":"320","author":"Malviya","year":"2023","journal-title":"Immunol Rev"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-009367","article-title":"Tumor-specific CD8+ T cells from the bone marrow resist exhaustion and exhibit increased persistence in tumor-bearing hosts as compared with tumor-infiltrating lymphocytes","volume":"13","author":"Zawidzka","year":"2025","journal-title":"J Immunother Cancer"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1016\/j.omton.2025.201044","article-title":"Targeting BCMA in multiple myeloma: A comprehensive review of immunotherapeutic strategies and clinical outcomes","volume":"33","author":"Chan","year":"2025","journal-title":"Mol Ther Oncol"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01653-8","article-title":"\u03b3\u03b4 T cells: origin and fate, subsets, diseases and immunotherapy","volume":"8","author":"Hu","year":"2023","journal-title":"Signal Transduct Target Ther"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1755096\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T05:33:19Z","timestamp":1774935199000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1755096\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,31]]},"references-count":129,"alternative-id":["10.3389\/fimmu.2026.1755096"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1755096","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,31]]},"article-number":"1755096"}}