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However, approximately half of the patients experience lymphoma progression after CD19 CAR T cell therapy. Immunosuppressive, M2\u2010like tumor\u2010associated macrophages (TAMs) contribute to the immunosuppressive tumor microenvironment (TME) and may facilitate resistance to CAR T cell therapy. Here, we identified folate receptor beta (FR\u03b2) as a specific marker of M2\u2010like TAMs and a predictor of poor survival in multiple independent DLBCL cohorts. Co\u2010culture studies of lymphoma\u2010macrophage spheroids revealed reciprocal interactions between lymphoma cells and M2\u2010like macrophages. Lymphoma cell co\u2010cultures promoted the differentiation of monocytes into M2\u2010like macrophages, while M2\u2010like macrophages fostered lymphoma cell growth and interfered with CD19 CAR T cell\u2010mediated killing of lymphoma cells. We demonstrated that M2\u2011like macrophages drive CAR T cells toward an exhausted phenotype and validated this finding using data from patients treated with CD19 CAR T cell therapy. Lastly, we generated FR\u03b2\u2010targeting CAR T cells and used them prior to CD19 CAR T cells to successfully improve lymphoma cell killing. Taken together, the results suggest active crosstalk between lymphoma cells and M2\u2010like macrophages, as well as TAM\u2010mediated resistance mechanisms to CD19 CAR T cells, which can be circumvented by FR\u03b2 CAR T cells targeting the M2\u2010like TAMs. These results support the use of macrophage\u2010targeting to improve CAR T cell therapy outcomes in DLBCL.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hem3.70390","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T08:53:08Z","timestamp":1780044788000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Folate receptor beta targeting of tumor\u2010associated macrophages improves lymphoma cell responses to CD19 CAR T cells"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4223-1790","authenticated-orcid":false,"given":"Kerttu","family":"Kalander","sequence":"first","affiliation":[{"name":"Applied Tumor Genomics Research Program University of Helsinki Helsinki Finland"},{"name":"Translational Cancer Medicine Research Program University of Helsinki Helsinki Finland"},{"name":"iCAN Digital Precision Medicine Flagship Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8845-1887","authenticated-orcid":false,"given":"Katri","family":"Oksa","sequence":"additional","affiliation":[{"name":"Applied Tumor Genomics Research Program University of Helsinki Helsinki Finland"},{"name":"Translational Cancer Medicine Research Program University of Helsinki Helsinki Finland"},{"name":"iCAN Digital Precision Medicine Flagship Helsinki 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