{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T15:04:12Z","timestamp":1791731052403,"version":"4.3.4"},"reference-count":30,"publisher":"Rockefeller University Press","issue":"6","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,6,3]]},"abstract":"<jats:p>Fibroblast activation protein (FAP) is a candidate universal target antigen because it has been reported to be selectively expressed in nearly all solid tumors by a subset of immunosuppressive tumor stromal fibroblasts. We verified that 18\/18 human tumors of various histologies contained pronounced stromal elements staining strongly for FAP, and hypothesized that targeting tumor stroma with FAP-reactive T cells would inhibit tumor growth in cancer-bearing hosts. T cells genetically engineered with FAP-reactive chimeric antigen receptors (CARs) specifically degranulated and produced effector cytokines upon stimulation with FAP or FAP-expressing cell lines. However, adoptive transfer of FAP-reactive T cells into mice bearing a variety of subcutaneous tumors mediated limited antitumor effects and induced significant cachexia and lethal bone toxicities in two mouse strains. We found that FAP was robustly expressed on PDGFR-\u03b1+, Sca-1+ multipotent bone marrow stromal cells (BMSCs) in mice, as well as on well-characterized, clinical-grade multipotent human BMSCs. Accordingly, both mouse and human multipotent BMSCs were recognized by FAP-reactive T cells. The lethal bone toxicity and cachexia observed after cell-based immunotherapy targeting FAP cautions against its use as a universal target. Moreover, the expression of FAP by multipotent BMSCs may point toward the cellular origins of tumor stromal fibroblasts.<\/jats:p>","DOI":"10.1084\/jem.20130110","type":"journal-article","created":{"date-parts":[[2013,5,27]],"date-time":"2013-05-27T21:00:41Z","timestamp":1369688441000},"page":"1125-1135","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":443,"title":["Immune targeting of fibroblast activation protein triggers recognition of multipotent bone marrow stromal cells and cachexia"],"prefix":"10.1084","volume":"210","author":[{"given":"Eric","family":"Tran","sequence":"first","affiliation":[{"name":"Surgery Branch 1 and 2"},{"name":"Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhanalakshmi","family":"Chinnasamy","sequence":"additional","affiliation":[{"name":"Surgery Branch 1 and 2"},{"name":"Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiya","family":"Yu","sequence":"additional","affiliation":[{"name":"Surgery Branch 1 and 2"},{"name":"Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Morgan","sequence":"additional","affiliation":[{"name":"Surgery Branch 1 and 2"},{"name":"Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chyi-Chia Richard","family":"Lee","sequence":"additional","affiliation":[{"name":"Surgery Branch 1 and 2"},{"name":"Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas P.","family":"Restifo","sequence":"additional","affiliation":[{"name":"Surgery Branch 1 and 2"},{"name":"Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven A.","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Surgery Branch 1 and 2"},{"name":"Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2013,5,27]]},"reference":[{"key":"2023072601513003400_bib1","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1111\/j.1365-2141.2008.07241.x","article-title":"Fibroblast activation protein alpha identifies mesenchymal stromal cells from human bone marrow","volume":"142","author":"Bae","year":"2008","journal-title":"Br. 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