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We observed that some AML patient samples are resistant to killing by human-engineered cytotoxic CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Single-cell RNA-seq of primary AML samples and CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells before and after their interaction uncovered transcriptional programs that correlate with AML sensitivity or resistance to CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell killing. Resistance-associated AML programs were enriched in AML patients with poor survival, and killing-resistant AML cells did not engage T cells in vitro. Killing-sensitive AML potently activated T cells before being killed, and upregulated\n                    <jats:italic>ICAM1<\/jats:italic>\n                    , a key component of the immune synapse with T cells. Without ICAM1, killing-sensitive AML became resistant to killing by primary ex vivo-isolated CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in vitro, and engineered CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells in vitro and in vivo. While AML heterogeneity implies that multiple factors may determine their sensitivity to T cell killing, these data show that ICAM1 acts as an immune trigger, allowing T cell killing, and could play a role in AML patient survival in vivo.\n                  <\/jats:p>","DOI":"10.1038\/s41375-024-02255-1","type":"journal-article","created":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T15:02:21Z","timestamp":1715266941000},"page":"1246-1255","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["AML\/T cell interactomics uncover correlates of patient outcomes and the key role of ICAM1 in T cell killing of AML"],"prefix":"10.1038","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7588-1338","authenticated-orcid":false,"given":"Ece Canan","family":"Sayitoglu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogdan A.","family":"Luca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5087-1291","authenticated-orcid":false,"given":"Allison Paige","family":"Boss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin Craig","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert Arthur","family":"Freeborn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7033-6637","authenticated-orcid":false,"given":"Molly Javier","family":"Uyeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline Ping","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6943-3811","authenticated-orcid":false,"given":"Yusuke","family":"Nakauchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Waichler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4573-5118","authenticated-orcid":false,"given":"Norman","family":"Lacayo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Bacchetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5814-0984","authenticated-orcid":false,"given":"Ravindra","family":"Majeti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0941-9858","authenticated-orcid":false,"given":"Andrew J.","family":"Gentles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2862-1901","authenticated-orcid":false,"given":"Alma-Martina","family":"Cepika","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Roncarolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,9]]},"reference":[{"key":"2255_CR1","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1016\/j.bbmt.2018.06.010","volume":"24","author":"DA Jacobsohn","year":"2018","unstructured":"Jacobsohn DA, Loken MR, Fei M, Adams A, Brodersen LE, Logan BR, et al. 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RM is on the Advisory Boards of Kodikaz Therapeutic Solutions, Orbital Therapeutics, Pheast Therapeutics, and 858 Therapeutics. RM is a co-founder and equity holder of Pheast Therapeutics, MyeloGene, and Orbital Therapeutics. However, none of these companies had input into the design, execution, interpretation, or publication of the work in this manuscript. All other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}