{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T21:01:47Z","timestamp":1785013307741,"version":"3.55.0"},"reference-count":157,"publisher":"Begell House","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Crit Rev Oncog"],"published-print":{"date-parts":[[2026]]},"abstract":"<p>Chimeric antigen receptor T (CAR-T) cell therapies, based on introducing a genetically modified T cell receptor to a patient's T cells, have transformed the treatment of hematological tumors. However, their efficacy in solid tumors is limited to date. Among the multiple barriers that shape CAR-T cell efficacy, including antigen heterogeneity, hypoxic tumor microenvironment (TME), and immunosuppressive cell populations, the altered extracellular matrix (ECM) has emerged as a dominant but understudied obstacle. In this review, we summarize the key ECM alterations characteristic of solid tumors and highlight the physical and molecular features that limit CAR-T cell function and promote exhaustion. We further discuss strategies to overcome these constraints and therapy resistance, as well as approaches to assess CAR-T therapy efficacy in clinically relevant models.<\/p>","DOI":"10.1615\/critrevoncog.2026063896","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T16:10:59Z","timestamp":1773677459000},"page":"35-49","source":"Crossref","is-referenced-by-count":0,"title":["Review Article: The Extracellular Matrix as a Barrier for CAR-T Cell Therapy in Solid Tumors"],"prefix":"10.1615","volume":"31","author":[{"given":"Or-Yam","family":"Revach","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"613","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"Zhang M, Liu C, Tu J, Tang M, Ashrafizadeh M, Nabavi N, Sethi G, Zhao P, Liu S. Advances in cancer immunotherapy: Historical perspectives, current developments, and future directions. 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