{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:26:14Z","timestamp":1792553174989,"version":"4.5.0"},"reference-count":110,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004595","name":"Universiti Sains Malaysia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["amjmedsci.org","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The American Journal of the Medical Sciences"],"published-print":{"date-parts":[[2026,7]]},"DOI":"10.1016\/j.amjms.2026.03.016","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T03:40:10Z","timestamp":1774582810000},"page":"14-26","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"title":["CAR T cells engineered against LAG-3: Unleashing potency in the tumor microenvironment of breast cancer"],"prefix":"10.1016","volume":"372","author":[{"given":"Mohammad A.I.","family":"Al-Hatamleh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahasin","family":"Hamid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Vashisht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u2019mon M.","family":"Hatmal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Mussa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.amjms.2026.03.016_bib0001","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/s12943-023-01805-y","article-title":"Advancements in clinical aspects of targeted therapy and immunotherapy in breast cancer","volume":"22","author":"Ye","year":"2023","journal-title":"Mol Cancer"},{"issue":"14","key":"10.1016\/j.amjms.2026.03.016_bib0002","doi-asserted-by":"crossref","first-page":"7517","DOI":"10.3390\/ijms25147517","article-title":"Immunotherapy in breast cancer","volume":"25","author":"Dvir","year":"2024","journal-title":"Int J Mol Sci"},{"issue":"1","key":"10.1016\/j.amjms.2026.03.016_bib0003","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/s12943-024-01990-4","article-title":"Modulation of the tumor microenvironment and mechanism of immunotherapy-based drug resistance in breast cancer","volume":"23","author":"Kundu","year":"2024","journal-title":"Mol Cancer"},{"key":"10.1016\/j.amjms.2026.03.016_bib0004","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2024.1385571","article-title":"CAR-based immunotherapy for breast cancer: peculiarities, ongoing investigations, and future strategies","volume":"15","author":"Niu","year":"2024","journal-title":"Front Immunol"},{"issue":"9","key":"10.1016\/j.amjms.2026.03.016_bib0005","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s12032-023-02146-y","article-title":"Revolutionizing cancer treatment: a comprehensive review of CAR-T cell therapy","volume":"40","author":"Dabas","year":"2023","journal-title":"Med Oncol"},{"issue":"7","key":"10.1016\/j.amjms.2026.03.016_bib0006","doi-asserted-by":"crossref","first-page":"7844","DOI":"10.1002\/cam4.5551","article-title":"Chimeric antigen receptor T (CAR-T) cells: novel cell therapy for hematological malignancies","volume":"12","author":"Abbasi","year":"2023","journal-title":"Cancer Med"},{"issue":"1","key":"10.1016\/j.amjms.2026.03.016_bib0007","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s12943-023-01723-z","article-title":"CAR-cell therapy in the era of solid tumor treatment: current challenges and emerging therapeutic advances","volume":"22","author":"Maalej","year":"2023","journal-title":"Mol Cancer"},{"issue":"12","key":"10.1016\/j.amjms.2026.03.016_bib0008","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1038\/s41571-025-01075-1","article-title":"Optimizing CAR T cell therapy for solid tumours: a clinical perspective","volume":"22","author":"Li","year":"2025","journal-title":"Nat Rev Clin Oncol"},{"issue":"1","key":"10.1016\/j.amjms.2026.03.016_bib0009","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s00005-023-00684-x","article-title":"Updated clinical perspectives and challenges of chimeric antigen receptor-T cell therapy in colorectal cancer and invasive breast cancer","volume":"71","author":"Cao","year":"2023","journal-title":"Arch Immunol Ther Exp (Warsz)"},{"issue":"82","key":"10.1016\/j.amjms.2026.03.016_bib0010","doi-asserted-by":"crossref","first-page":"eabq3016","DOI":"10.1126\/sciimmunol.abq3016","article-title":"Metabolic challenges and interventions in CAR T cell therapy","volume":"8","author":"Peng","year":"2023","journal-title":"Sci Immunol"},{"key":"10.1016\/j.amjms.2026.03.016_bib0011","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2024.105266","article-title":"Advancements and challenges in developing in vivo CAR T cell therapies for cancer treatment","volume":"106","author":"Bui","year":"2024","journal-title":"EBioMedicine"},{"issue":"1","key":"10.1016\/j.amjms.2026.03.016_bib0012","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s13045-023-01492-8","article-title":"Challenges and new technologies in adoptive cell therapy","volume":"16","author":"Zhang","year":"2023","journal-title":"J Hematol Oncol"},{"key":"10.1016\/j.amjms.2026.03.016_bib0013","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.956090","article-title":"The promising immune checkpoint LAG-3 in cancer immunotherapy: from basic research to clinical application","volume":"13","author":"Huo","year":"2022","journal-title":"Front Immunol"},{"issue":"1","key":"10.1016\/j.amjms.2026.03.016_bib0014","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/imr.12519","article-title":"LAG3 (CD223) as a cancer immunotherapy target","volume":"276","author":"Andrews","year":"2017","journal-title":"Immunol Rev"},{"issue":"5","key":"10.1016\/j.amjms.2026.03.016_bib0015","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2024.107241","article-title":"The immune checkpoint receptor LAG3: structure, function, and target for cancer immunotherapy","volume":"300","author":"Mariuzza","year":"2024","journal-title":"J Biol Chem"},{"issue":"1","key":"10.1016\/j.amjms.2026.03.016_bib0016","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/s13045-023-01499-1","article-title":"Targeting LAG-3, TIM-3, and TIGIT for cancer immunotherapy","volume":"16","author":"Cai","year":"2023","journal-title":"J Hematol Oncol"},{"issue":"9","key":"10.1016\/j.amjms.2026.03.016_bib0017","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1038\/s41590-023-01569-z","article-title":"LAG-3 as the third checkpoint inhibitor","volume":"24","author":"Aggarwal","year":"2023","journal-title":"Nat Immunol"},{"issue":"10","key":"10.1016\/j.amjms.2026.03.016_bib0018","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22105282","article-title":"Understanding LAG-3 signaling","volume":"22","author":"Chocarro","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"7","key":"10.1016\/j.amjms.2026.03.016_bib0019","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.tips.2025.05.008","article-title":"Exploring new frontiers in LAG-3 biology and therapeutics","volume":"46","author":"Wang","year":"2025","journal-title":"Trends Pharmacol. Sci"},{"issue":"2","key":"10.1016\/j.amjms.2026.03.016_bib0020","doi-asserted-by":"crossref","first-page":"1","DOI":"10.12968\/hmed.2021.0459","article-title":"Breast cancer: presentation, investigation and management","volume":"83","author":"Katsura","year":"2022","journal-title":"Br J Hosp Med (Lond)"},{"issue":"1130","key":"10.1016\/j.amjms.2026.03.016_bib0021","doi-asserted-by":"crossref","DOI":"10.1259\/bjr.20211033","article-title":"Understanding breast cancer as a global health concern","volume":"95","author":"Wilkinson","year":"2022","journal-title":"Br J Radiol"},{"issue":"1","key":"10.1016\/j.amjms.2026.03.016_bib0022","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s41392-024-02108-4","article-title":"Breast cancer: pathogenesis and treatments","volume":"10","author":"Xiong","year":"2025","journal-title":"Signal Transduct Target Ther"},{"issue":"1","key":"10.1016\/j.amjms.2026.03.016_bib0023","doi-asserted-by":"crossref","first-page":"46","DOI":"10.5858\/arpa.2022-0070-RA","article-title":"Molecular classification of breast cancer: relevance and challenges","volume":"147","author":"Zhang","year":"2023","journal-title":"Arch Pathol Lab Med"},{"key":"10.1016\/j.amjms.2026.03.016_bib0024","doi-asserted-by":"crossref","first-page":"359","DOI":"10.2340\/1651-226X.2024.33008","article-title":"The tumor immune microenvironment in breast cancer progression","volume":"63","author":"Otterlei Fj\u00f8rtoft","year":"2024","journal-title":"Acta Oncol"},{"issue":"23","key":"10.1016\/j.amjms.2026.03.016_bib0025","doi-asserted-by":"crossref","DOI":"10.3390\/ijms242316771","article-title":"Targeting the tumor microenvironment in breast cancer: prognostic and predictive significance and therapeutic opportunities","volume":"24","author":"Dom\u00ednguez-Cejudo","year":"2023","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.amjms.2026.03.016_bib0026","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2023.1198826","article-title":"Identification of disulfidptosis-related subtypes, characterization of tumor microenvironment infiltration, and development of a prognosis model in breast cancer","volume":"14","author":"Liang","year":"2023","journal-title":"Front Immunol"},{"key":"10.1016\/j.amjms.2026.03.016_bib0027","article-title":"Molecular and clinical characterization of LAG3 in breast cancer through 2994 samples","volume":"12","author":"Liu","year":"2021","journal-title":"Front Immunol"},{"issue":"1","key":"10.1016\/j.amjms.2026.03.016_bib0028","doi-asserted-by":"crossref","first-page":"142","DOI":"10.55730\/1300-0144.5567","article-title":"LAG-3 expression in tumor microenvironment of triple-negative breast cancer","volume":"53","author":"Tahtac\u0131","year":"2023","journal-title":"Turk J Med Sci"},{"issue":"1","key":"10.1016\/j.amjms.2026.03.016_bib0029","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1097\/PAI.0000000000000954","article-title":"Prognostic and clinicopathologic associations of LAG-3 expression in triple-negative breast cancer","volume":"30","author":"Stovgaard","year":"2022","journal-title":"Appl Immunohistochem Mol Morphol"},{"issue":"12","key":"10.1016\/j.amjms.2026.03.016_bib0030","doi-asserted-by":"crossref","first-page":"2977","DOI":"10.1093\/annonc\/mdx557","article-title":"LAG-3+ tumor infiltrating lymphocytes in breast cancer: clinical correlates and association with PD-1\/PD-L1+ tumors","volume":"28","author":"Burugu","year":"2017","journal-title":"Annals Oncol"},{"key":"10.1016\/j.amjms.2026.03.016_bib0031","article-title":"LAG-3(+) tumor-infiltrating lymphocytes ameliorates overall survival in triple-negative breast cancer patients","volume":"12","author":"Hu","year":"2022","journal-title":"Front Oncol"},{"issue":"1","key":"10.1016\/j.amjms.2026.03.016_bib0032","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1186\/s12957-022-02810-z","article-title":"High co-expression of immune checkpoint receptors PD-1, CTLA-4, LAG-3, TIM-3, and TIGIT on tumor-infiltrating lymphocytes in early-stage breast cancer","volume":"20","author":"Mollavelioglu","year":"2022","journal-title":"World J Surg Oncol"},{"issue":"10","key":"10.1016\/j.amjms.2026.03.016_bib0033","doi-asserted-by":"crossref","first-page":"2656","DOI":"10.3390\/biomedicines10102656","article-title":"Prognostic impact of LAG-3 mRNA expression in early breast cancer","volume":"10","author":"Heimes","year":"2022","journal-title":"Biomedicines"},{"issue":"2","key":"10.1016\/j.amjms.2026.03.016_bib0034","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2020-001014","article-title":"LAG-3: from molecular functions to clinical applications","volume":"8","author":"Maruhashi","year":"2020","journal-title":"J Immunother Cancer"},{"key":"10.1016\/j.amjms.2026.03.016_bib0035","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1146\/annurev-cancerbio-042920-104912","article-title":"The multifaceted role of regulatory T cells in breast cancer","volume":"5","author":"Kos","year":"2021","journal-title":"Annu Rev Cancer Biol"},{"issue":"8","key":"10.1016\/j.amjms.2026.03.016_bib0036","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0182786","article-title":"Expression of the MHC class II in triple-negative breast cancer is associated with tumor-infiltrating lymphocytes and interferon signaling","volume":"12","author":"Park","year":"2017","journal-title":"PLOS ONE"},{"issue":"2","key":"10.1016\/j.amjms.2026.03.016_bib0037","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s00262-018-2262-5","article-title":"The expression of MHC class II molecules on murine breast tumors delays T-cell exhaustion, expands the T-cell repertoire, and slows tumor growth","volume":"68","author":"McCaw","year":"2019","journal-title":"Cancer Immunol Immunother"},{"issue":"9","key":"10.1016\/j.amjms.2026.03.016_bib0038","doi-asserted-by":"crossref","first-page":"2256","DOI":"10.1093\/jimmun\/vkaf120","article-title":"LAG3-MHCII interaction induces a tight cell-cell interface at the immunological synapse","volume":"214","author":"Wang","year":"2025","journal-title":"J Immunol"},{"issue":"1","key":"10.1016\/j.amjms.2026.03.016_bib0039","doi-asserted-by":"crossref","DOI":"10.1111\/imr.70002","article-title":"LAG time in the era of immunotherapy\u2014New molecular insights into the immunosuppression mechanism of lymphocyte activation gene-3","volume":"330","author":"Luca","year":"2025","journal-title":"Immunol. Rev."},{"issue":"4","key":"10.1016\/j.amjms.2026.03.016_bib0040","doi-asserted-by":"crossref","DOI":"10.3390\/biomedicines12040763","article-title":"Tumor-infiltrating lymphocytes (TILs) in breast cancer: prognostic and predictive significance across molecular subtypes","volume":"12","author":"Ciarka","year":"2024","journal-title":"Biomedicines"},{"key":"10.1016\/j.amjms.2026.03.016_bib0041","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2025.117194","article-title":"Transforming the \u201ccold\u201d tumors to \u201chot\u201d tumors: strategies for immune activation","volume":"241","author":"Kong","year":"2025","journal-title":"Biochem. Pharmacol"},{"issue":"2","key":"10.1016\/j.amjms.2026.03.016_bib0042","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/sj.emboj.7601520","article-title":"Metalloproteases regulate T-cell proliferation and effector function via LAG-3","volume":"26","author":"Li","year":"2007","journal-title":"Embo j"},{"issue":"23","key":"10.1016\/j.amjms.2026.03.016_bib0043","doi-asserted-by":"crossref","first-page":"5030","DOI":"10.1158\/1078-0432.CCR-21-2390","article-title":"Molecular pathways and mechanisms of LAG3 in cancer therapy","volume":"28","author":"Andrews","year":"2022","journal-title":"Clinical Cancer Research"},{"key":"10.1016\/j.amjms.2026.03.016_bib0044","doi-asserted-by":"crossref","DOI":"10.1016\/j.smim.2019.101305","article-title":"Lymphocyte-activation gene 3 (LAG3): the next immune checkpoint receptor","volume":"42","author":"Ruffo","year":"2019","journal-title":"Semin. Immunol"},{"issue":"1","key":"10.1016\/j.amjms.2026.03.016_bib0045","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22010379","article-title":"LAG-3, TIM-3 and VISTA expression on tumor-infiltrating lymphocytes in oropharyngeal squamous cell carcinoma-potential biomarkers for targeted therapy concepts","volume":"22","author":"Wuerdemann","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"4","key":"10.1016\/j.amjms.2026.03.016_bib0046","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.ccell.2025.02.026","article-title":"Distinct CD8(+) T cell dynamics associate with response to neoadjuvant cancer immunotherapies","volume":"43","author":"Li","year":"2025","journal-title":"Cancer Cell"},{"issue":"2","key":"10.1016\/j.amjms.2026.03.016_bib0047","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/mi.2013.62","article-title":"Highly prevalent colorectal cancer-infiltrating LAP+ Foxp3\u2212 T cells exhibit more potent immunosuppressive activity than Foxp3+ regulatory T cells","volume":"7","author":"Scurr","year":"2014","journal-title":"Mucosal Immunol"},{"issue":"6","key":"10.1016\/j.amjms.2026.03.016_bib0048","doi-asserted-by":"crossref","DOI":"10.1080\/2162402X.2015.1008355","article-title":"Tumor-infiltrating plasmacytoid dendritic cells promote immunosuppression by Tr1 cells in human liver tumors","volume":"4","author":"Pedroza-Gonzalez","year":"2015","journal-title":"Oncoimmunology"},{"issue":"1","key":"10.1016\/j.amjms.2026.03.016_bib0049","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1186\/s40364-024-00671-0","article-title":"Deciphering LAG-3: unveiling molecular mechanisms and clinical advancements","volume":"12","author":"Mart\u00ednez-P\u00e9rez","year":"2024","journal-title":"Biomark Res"},{"issue":"5","key":"10.1016\/j.amjms.2026.03.016_bib0050","doi-asserted-by":"crossref","first-page":"207","DOI":"10.3892\/ol.2020.12070","article-title":"Progress of immune checkpoint LAG-3 in immunotherapy","volume":"20","author":"Shan","year":"2020","journal-title":"Oncol Lett"},{"key":"10.1016\/j.amjms.2026.03.016_bib0051","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.jim.2018.02.003","article-title":"Establishment of engineered cell-based assays mediating LAG3 and PD1 immune suppression enables potency measurement of blocking antibodies and assessment of signal transduction","volume":"456","author":"Bhagwat","year":"2018","journal-title":"J. Immunol. Methods"},{"issue":"7","key":"10.1016\/j.amjms.2026.03.016_bib0052","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1038\/s41590-022-01238-7","article-title":"LAG3 ectodomain structure reveals functional interfaces for ligand and antibody recognition","volume":"23","author":"Ming","year":"2022","journal-title":"Nat. Immunol"},{"issue":"9","key":"10.1016\/j.amjms.2026.03.016_bib0053","doi-asserted-by":"crossref","first-page":"2354","DOI":"10.1016\/j.cell.2025.02.014","article-title":"Ligand-induced ubiquitination unleashes LAG3 immune checkpoint function by hindering membrane sequestration of signaling motifs","volume":"188","author":"Jiang","year":"2025","journal-title":"Cell"},{"key":"10.1016\/j.amjms.2026.03.016_bib0054","article-title":"LAG3\u2019s Enigmatic mechanism of action","volume":"11","author":"Graydon","year":"2020","journal-title":"Front Immunol"},{"issue":"5-6","key":"10.1016\/j.amjms.2026.03.016_bib0055","doi-asserted-by":"crossref","first-page":"176","DOI":"10.18632\/genesandcancer.180","article-title":"The promising immune checkpoint LAG-3: from tumor microenvironment to cancer immunotherapy","volume":"9","author":"Long","year":"2018","journal-title":"Genes Cancer"},{"issue":"5","key":"10.1016\/j.amjms.2026.03.016_bib0056","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1038\/s41590-022-01176-4","article-title":"LAG3 associates with TCR\u2013CD3 complexes and suppresses signaling by driving co-receptor\u2013Lck dissociation","volume":"23","author":"Guy","year":"2022","journal-title":"Nat. Immunol"},{"issue":"15","key":"10.1016\/j.amjms.2026.03.016_bib0057","doi-asserted-by":"crossref","first-page":"6017","DOI":"10.1074\/jbc.RA119.007455","article-title":"Atypical motifs in the cytoplasmic region of the inhibitory immune co-receptor LAG-3 inhibit T cell activation","volume":"294","author":"Maeda","year":"2019","journal-title":"J Biolo Chem"},{"issue":"11","key":"10.1016\/j.amjms.2026.03.016_bib0058","doi-asserted-by":"crossref","first-page":"3383","DOI":"10.1172\/JCI31184","article-title":"LAG-3 regulates CD8+ T cell accumulation and effector function in murine self- and tumor-tolerance systems","volume":"117","author":"Grosso","year":"2007","journal-title":"J Clin Invest"},{"issue":"6","key":"10.1016\/j.amjms.2026.03.016_bib0059","doi-asserted-by":"crossref","first-page":"e1792","DOI":"10.1038\/cddis.2015.162","article-title":"T-cell exhaustion in the tumor microenvironment","volume":"6","author":"Jiang","year":"2015","journal-title":"Cell Death Dis"},{"key":"10.1016\/j.amjms.2026.03.016_bib0060","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2024.1507283","article-title":"CD8(+) T cell exhaustion in the tumor microenvironment of breast cancer","volume":"15","author":"Xie","year":"2024","journal-title":"Front Immunol"},{"issue":"6","key":"10.1016\/j.amjms.2026.03.016_bib0061","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1080\/13543784.2022.2054326","article-title":"CAR-T cell therapy for triple-negative breast cancer and other solid tumors: preclinical and clinical progress","volume":"31","author":"Corti","year":"2022","journal-title":"Expert Opin Investig Drugs"},{"issue":"12","key":"10.1016\/j.amjms.2026.03.016_bib0062","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1158\/1535-7163.MCT-20-0385","article-title":"Emerging CAR-T cell therapy for the treatment of triple-negative breast cancer","volume":"19","author":"Dees","year":"2020","journal-title":"Mol Cancer Ther"},{"issue":"1","key":"10.1016\/j.amjms.2026.03.016_bib0063","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s12943-022-01712-8","article-title":"CAR T cells: engineering immune cells to treat brain cancers and beyond","volume":"22","author":"Huang","year":"2023","journal-title":"Mol Cancer"},{"issue":"21","key":"10.1016\/j.amjms.2026.03.016_bib0064","doi-asserted-by":"crossref","DOI":"10.3390\/ijms242115688","article-title":"CAR-T cell therapy: from the shop to cancer therapy","volume":"24","author":"Uscanga-Palomeque","year":"2023","journal-title":"Int J Mol Sci"},{"issue":"12","key":"10.1016\/j.amjms.2026.03.016_bib0065","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.3390\/cells12121606","article-title":"Recent advances in CAR-based solid tumor immunotherapy","volume":"12","author":"Shin","year":"2023","journal-title":"Cells"},{"issue":"6","key":"10.1016\/j.amjms.2026.03.016_bib0066","doi-asserted-by":"crossref","DOI":"10.1080\/21645515.2022.2114254","article-title":"Current updates on generations, approvals, and clinical trials of CAR T-cell therapy","volume":"18","author":"Asmamaw Dejenie","year":"2022","journal-title":"Hum Vaccin Immunother"},{"issue":"8","key":"10.1016\/j.amjms.2026.03.016_bib0067","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1517\/14712598.2015.1046430","article-title":"TRUCKs: the fourth generation of CARs","volume":"15","author":"Chmielewski","year":"2015","journal-title":"Expert Opin Biol Ther"},{"key":"10.1016\/j.amjms.2026.03.016_bib0068","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2025.1574742","article-title":"CAR-NK cell therapy: promise and challenges in solid tumors","volume":"16","author":"Balkhi","year":"2025","journal-title":"Front Immunol"},{"issue":"1","key":"10.1016\/j.amjms.2026.03.016_bib0069","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s41571-023-00832-4","article-title":"CAR T cell therapy for patients with solid tumours: key lessons to learn and unlearn","volume":"21","author":"Albelda","year":"2024","journal-title":"Nat Rev Clin Oncol"},{"issue":"7971","key":"10.1016\/j.amjms.2026.03.016_bib0070","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1038\/s41586-023-06243-w","article-title":"CAR T therapy beyond cancer: the evolution of a living drug","volume":"619","author":"Baker","year":"2023","journal-title":"Nature"},{"issue":"6","key":"10.1016\/j.amjms.2026.03.016_bib0071","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/s41591-018-0041-7","article-title":"CAR T cell-induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade","volume":"24","author":"Giavridis","year":"2018","journal-title":"Nat Med"},{"issue":"26","key":"10.1016\/j.amjms.2026.03.016_bib0072","doi-asserted-by":"crossref","first-page":"3321","DOI":"10.1182\/blood-2016-04-703751","article-title":"Toxicities of chimeric antigen receptor T cells: recognition and management","volume":"127","author":"Brudno","year":"2016","journal-title":"Blood"},{"issue":"6382","key":"10.1016\/j.amjms.2026.03.016_bib0073","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1126\/science.aar6711","article-title":"CAR T cell immunotherapy for human cancer","volume":"359","author":"June","year":"2018","journal-title":"Science"},{"issue":"1","key":"10.1016\/j.amjms.2026.03.016_bib0074","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1093\/neuonc\/noaa183","article-title":"Immune effector cell-associated neurotoxicity syndrome after chimeric antigen receptor T-cell therapy for lymphoma: predictive biomarkers and clinical outcomes","volume":"23","author":"Holtzman","year":"2021","journal-title":"Neuro Oncol"},{"issue":"7","key":"10.1016\/j.amjms.2026.03.016_bib0075","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.jtct.2023.03.006","article-title":"Immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome","volume":"29","author":"Hines","year":"2023","journal-title":"Transplant Cell Ther"},{"issue":"2","key":"10.1016\/j.amjms.2026.03.016_bib0076","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s11899-023-00687-7","article-title":"CAR-T cell therapy: the efficacy and toxicity balance","volume":"18","author":"Chohan","year":"2023","journal-title":"Curr Hematol Malig Rep"},{"issue":"7","key":"10.1016\/j.amjms.2026.03.016_bib0077","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.jtct.2023.04.001","article-title":"Anakinra for refractory cytokine release syndrome or Immune effector cell-associated neurotoxicity syndrome after chimeric antigen receptor T cell therapy","volume":"29","author":"Gazeau","year":"2023","journal-title":"Transplant Cell Ther"},{"issue":"1","key":"10.1016\/j.amjms.2026.03.016_bib0078","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1186\/s13046-024-03218-1","article-title":"Understanding the role of TNFR2 signaling in the tumor microenvironment of breast cancer","volume":"43","author":"Mussa","year":"2024","journal-title":"J Exp Clin Cancer Res"},{"key":"10.1016\/j.amjms.2026.03.016_bib0079","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.blre.2018.11.002","article-title":"Recent advances in CAR T-cell toxicity: mechanisms, manifestations and management","volume":"34","author":"Brudno","year":"2019","journal-title":"Blood Rev"},{"issue":"1","key":"10.1016\/j.amjms.2026.03.016_bib0080","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s41571-022-00704-3","article-title":"Overcoming on-target, off-tumour toxicity of CAR T cell therapy for solid tumours","volume":"20","author":"Flugel","year":"2023","journal-title":"Nat Rev Clin Oncol"},{"issue":"4","key":"10.1016\/j.amjms.2026.03.016_bib0081","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41408-021-00459-7","article-title":"CAR-T cell therapy: current limitations and potential strategies","volume":"11","author":"Sterner","year":"2021","journal-title":"Blood Cancer J"},{"issue":"6","key":"10.1016\/j.amjms.2026.03.016_bib0082","doi-asserted-by":"crossref","first-page":"2609","DOI":"10.7150\/ijbs.70120","article-title":"CAR-T cell therapy for breast cancer: from basic research to clinical application","volume":"18","author":"Yang","year":"2022","journal-title":"Int J Biol Sci"},{"issue":"4","key":"10.1016\/j.amjms.2026.03.016_bib0083","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.ccell.2025.03.019","article-title":"CAR-T therapy in solid tumors","volume":"43","author":"Du","year":"2025","journal-title":"Cancer Cell"},{"issue":"3","key":"10.1016\/j.amjms.2026.03.016_bib0084","doi-asserted-by":"crossref","DOI":"10.1200\/EDBK-25-473440","article-title":"Autologous T-Cell Therapies in Solid Tumor Malignancies: Current Landscape and Future Opportunities","volume":"45","author":"Reinhorn","year":"2025","journal-title":"Am Soc Clin Oncol Educ Book"},{"issue":"2","key":"10.1016\/j.amjms.2026.03.016_bib0085","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41388-020-01501-x","article-title":"Counteracting CAR T cell dysfunction","volume":"40","author":"Poorebrahim","year":"2021","journal-title":"Oncogene"},{"key":"10.1016\/j.amjms.2026.03.016_bib0086","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2022.1034257","article-title":"Mechanisms of CAR T cell exhaustion and current counteraction strategies","volume":"10","author":"Zhu","year":"2022","journal-title":"Front Cell Dev Biol"},{"issue":"1","key":"10.1016\/j.amjms.2026.03.016_bib0087","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1186\/s12967-022-03442-3","article-title":"Exhaustion of CAR T cells: potential causes and solutions","volume":"20","author":"Kouro","year":"2022","journal-title":"J Transl Med"},{"key":"10.1016\/j.amjms.2026.03.016_bib0088","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2022.103941","article-title":"Improving CAR-T immunotherapy: overcoming the challenges of T cell exhaustion","volume":"77","author":"Gumber","year":"2022","journal-title":"eBioMedicine"},{"key":"10.1016\/j.amjms.2026.03.016_bib0089","first-page":"95","article-title":"Armored CAR T-cells: the next chapter in T-cell cancer immunotherapy","volume":"15","author":"Hawkins","year":"2021","journal-title":"Biologics"},{"key":"10.1016\/j.amjms.2026.03.016_bib0090","article-title":"Relatlimab: a novel drug targeting immune checkpoint LAG-3 in melanoma therapy","volume":"14","author":"Su","year":"2023","journal-title":"Front Pharmacol"},{"key":"10.1016\/j.amjms.2026.03.016_bib0091","doi-asserted-by":"crossref","DOI":"10.1016\/j.ctrv.2024.102868","article-title":"CAR-T cell therapy for breast cancer: current status and future perspective","volume":"133","author":"Buono","year":"2025","journal-title":"Cancer Treat. Rev"},{"key":"10.1016\/j.amjms.2026.03.016_bib0092","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2024.116782","article-title":"A novel LAG3 neutralizing antibody improves cancer immunotherapy by dual inhibition of MHC-II and FGL1 ligand binding","volume":"175","author":"Zuo","year":"2024","journal-title":"Biomed Pharmacother"},{"issue":"1","key":"10.1016\/j.amjms.2026.03.016_bib0093","doi-asserted-by":"crossref","first-page":"4109","DOI":"10.1038\/s41467-019-11893-4","article-title":"Engineered triple inhibitory receptor resistance improves anti-tumor CAR-T cell performance via CD56","volume":"10","author":"Zou","year":"2019","journal-title":"Nat Commun"},{"issue":"1","key":"10.1016\/j.amjms.2026.03.016_bib0094","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s12943-022-01559-z","article-title":"Engineering the next-generation of CAR T-cells with CRISPR-Cas9 gene editing","volume":"21","author":"Dimitri","year":"2022","journal-title":"Mol. Cancer"},{"issue":"1","key":"10.1016\/j.amjms.2026.03.016_bib0095","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s40364-024-00602-z","article-title":"CRISPR\/Cas-based CAR-T cells: production and application","volume":"12","author":"Song","year":"2024","journal-title":"Biomark Res"},{"issue":"12","key":"10.1016\/j.amjms.2026.03.016_bib0096","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1038\/s41375-024-02444-y","article-title":"Leveraging CRISPR gene editing technology to optimize the efficacy, safety and accessibility of CAR T-cell therapy","volume":"38","author":"Lei","year":"2024","journal-title":"Leukemia"},{"issue":"7","key":"10.1016\/j.amjms.2026.03.016_bib0097","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1016\/j.ymthe.2018.05.003","article-title":"Dominant-negative TGF-\u03b2 receptor enhances PSMA-targeted Human CAR T cell proliferation and augments prostate cancer eradication","volume":"26","author":"Kloss","year":"2018","journal-title":"Molecular Therapy"},{"issue":"10","key":"10.1016\/j.amjms.2026.03.016_bib0098","doi-asserted-by":"crossref","first-page":"3522","DOI":"10.1016\/j.ymthe.2024.07.020","article-title":"Armored bicistronic CAR T cells with dominant-negative TGF-\u03b2 receptor II to overcome resistance in glioblastoma","volume":"32","author":"Li","year":"2024","journal-title":"Mol Ther"},{"key":"10.1016\/j.amjms.2026.03.016_bib0099","doi-asserted-by":"crossref","DOI":"10.1016\/j.omtn.2023.102038","article-title":"Efficient shRNA-based knockdown of multiple target genes for cell therapy using a chimeric miRNA cluster platform","volume":"34","author":"Rossi","year":"2023","journal-title":"Molecular Therapy Nucleic Acids"},{"issue":"6","key":"10.1016\/j.amjms.2026.03.016_bib0100","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1007\/s11912-023-01406-4","article-title":"The latest option: Nivolumab and Relatlimab in advanced melanoma","volume":"25","author":"Albrecht","year":"2023","journal-title":"Curr Oncol Rep"},{"issue":"11","key":"10.1016\/j.amjms.2026.03.016_bib0101","doi-asserted-by":"crossref","first-page":"102353","DOI":"10.1016\/j.xcrm.2025.102353","article-title":"CAR-T cells in solid tumors: Challenges and breakthroughs","volume":"6","author":"Escobar","year":"2025","journal-title":"Cell Rep Med"},{"issue":"19","key":"10.1016\/j.amjms.2026.03.016_bib0102","doi-asserted-by":"crossref","DOI":"10.3390\/cancers17193172","article-title":"Regulatory T cells in invasive breast cancer: prognosis, mechanisms and therapy","volume":"17","author":"Xu","year":"2025","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.amjms.2026.03.016_bib0103","doi-asserted-by":"crossref","DOI":"10.1016\/j.canlet.2025.217865","article-title":"The role of tumor microenvironment and immune cell crosstalk in triple-negative breast cancer (TNBC): emerging therapeutic opportunities","volume":"628","author":"Sabit","year":"2025","journal-title":"Cancer Lett"},{"issue":"1","key":"10.1016\/j.amjms.2026.03.016_bib0104","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-025-95114-7","article-title":"Thymidine kinase 1 concentration and activity in metastatic breast cancer under CDK4\/6 inhibitor therapy","volume":"15","author":"Moukas","year":"2025","journal-title":"Sci Rep"},{"issue":"3","key":"10.1016\/j.amjms.2026.03.016_bib0105","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1016\/j.ymthe.2025.12.025","article-title":"DR5 CAR-T cells target melanoma and suppress MDSCs with minimal toxicity","volume":"34","author":"Wang","year":"2025","journal-title":"Mol Ther"},{"issue":"1","key":"10.1016\/j.amjms.2026.03.016_bib0106","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/s41392-024-01937-7","article-title":"Pre-metastatic niche: formation, characteristics and therapeutic implication","volume":"9","author":"Wang","year":"2024","journal-title":"Signal Transduct Target Ther"},{"key":"10.1016\/j.amjms.2026.03.016_bib0107","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2023.1172681","article-title":"Stromal depletion by TALEN-edited universal hypoimmunogenic FAP-CAR T cells enables infiltration and anti-tumor cytotoxicity of tumor antigen-targeted CAR-T immunotherapy","volume":"14","author":"Das","year":"2023","journal-title":"Front Immunol"},{"key":"10.1016\/j.amjms.2026.03.016_bib0108","doi-asserted-by":"crossref","DOI":"10.1177\/20503121211069012","article-title":"Tumor promoting roles of IL-10, TGF-\u03b2, IL-4, and IL-35: its implications in cancer immunotherapy","volume":"10","author":"Mirlekar","year":"2022","journal-title":"SAGE Open Med"},{"issue":"2","key":"10.1016\/j.amjms.2026.03.016_bib0109","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1136\/gutjnl-2021-325808","article-title":"Blockade of interleukin 10 potentiates antitumour immune function in human colorectal cancer liver metastases","volume":"72","author":"Sullivan","year":"2023","journal-title":"Gut"},{"issue":"1","key":"10.1016\/j.amjms.2026.03.016_bib0110","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1186\/s12935-024-03315-3","article-title":"Current challenges and therapeutic advances of CAR-T cell therapy for solid tumors","volume":"24","author":"Chen","year":"2024","journal-title":"Cancer Cell Int."}],"container-title":["The American Journal of the Medical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002962926001199?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002962926001199?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T13:32:55Z","timestamp":1781184775000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0002962926001199"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":110,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["S0002962926001199"],"URL":"https:\/\/doi.org\/10.1016\/j.amjms.2026.03.016","relation":{},"ISSN":["0002-9629"],"issn-type":[{"value":"0002-9629","type":"print"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"CAR T cells engineered against LAG-3: Unleashing potency in the tumor microenvironment of breast cancer","name":"articletitle","label":"Article Title"},{"value":"The American Journal of the Medical Sciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.amjms.2026.03.016","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Inc. on behalf of Southern Society for Clinical Investigation.","name":"copyright","label":"Copyright"}]}}