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We devised multiplex immunostaining and ISH assays to interrogate CAR T cells and other immune cell infiltrates in biopsies of diffuse large B cell lymphoma following axicabtagene ciloleucel infusion. We found that a majority of intratumoral CAR T cells expressed markers of T cell activation but, unexpectedly, constituted \u22645% of all T cells within the TME 5 days or more after therapy. Large numbers of T cells without CAR were also activated within the TME after axicabtagene ciloleucel infusion; these cells were positive for Ki-67, IFN-\u03b3, granzyme B (GzmB), and\/or PD-1 and were found at the highest levels in biopsies with CAR T cells. Additionally, non-CAR immune cells were the exclusive source of IL-6, a cytokine associated with cytokine release syndrome, and were found at their highest numbers in biopsies with CAR T cells. These data suggest that intratumoral CAR T cells are associated with non-CAR immune cell activation within the TME with both beneficial and pathological effects.<\/jats:p>","DOI":"10.1172\/jci.insight.134612","type":"journal-article","created":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T14:19:57Z","timestamp":1591107597000},"source":"Crossref","is-referenced-by-count":102,"title":["Activation of CAR and non-CAR T cells within the tumor microenvironment following CAR T cell therapy"],"prefix":"10.1172","volume":"5","author":[{"given":"Pei-Hsuan","family":"Chen","sequence":"first","affiliation":[{"name":"Center for Immuno-Oncology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikel","family":"Lipschitz","sequence":"additional","affiliation":[{"name":"Center for Immuno-Oncology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0556-0616","authenticated-orcid":true,"given":"Jason L.","family":"Weirather","sequence":"additional","affiliation":[{"name":"Center for Immuno-Oncology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caron","family":"Jacobson","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Armand","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2816-0260","authenticated-orcid":true,"given":"Kyle","family":"Wright","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. 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