{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:23:01Z","timestamp":1791937381831,"version":"4.3.4"},"reference-count":45,"publisher":"American Society of Hematology","issue":"14","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,7,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Tumor-associated macrophages (TAMs) are recognized as a hallmark of certain solid cancers and predictors of poor prognosis; however, the functional role of TAMs in lymphoid malignancies, including B-cell lymphoma, has not been well defined. We identified infiltration of F4\/80+ TAMs in a syngeneic mouse model using the recently generated murine mantle cell lymphoma (MCL) cell line FC-muMCL1. Multicolor flow cytometric analysis of syngeneic lymphoma tumors showed distinct polarization of F4\/80+ TAMs into CD206+ M2 and CD80+ M1 phenotypes. Using human MCL cell lines (Mino, Granta, and JVM2), we further showed that MCL cells polarized monocyte-derived macrophages toward an M2-like phenotype, as assessed by CD163+ expression and increased interleukin-10 (IL-10) level; however, levels of the M1 markers CD80 and IL-12 remained unaffected. To show that macrophages contribute to MCL tumorigenesis, we xenografted the human MCL cell line Mino along with CD14+ monocytes and compared tumor growth between these 2 groups. Results showed that xenografted Mino along with CD14+ monocytes significantly increased the tumor growth in vivo compared with MCL cells alone (P &amp;lt; .001), whereas treatment with liposomal clodronate (to deplete the macrophages) reversed the effect of CD14+ monocytes on growth of MCL xenografts (P &amp;lt; .001). Mechanistically, IL-10 secreted by MCL-polarized M2-like macrophages was found to be responsible for increasing MCL growth by activating STAT1 signaling, whereas IL-10 neutralizing antibody or STAT1 inhibition by fludarabine or STAT1 short hairpin RNA significantly abolished MCL growth (P &amp;lt; .01). Collectively, our data show the existence of a tumor microenvironmental network of macrophages and MCL tumor and suggest the importance of macrophages in interventional therapeutic strategies against MCL and other lymphoid malignancies.<\/jats:p>","DOI":"10.1182\/bloodadvances.2020003871","type":"journal-article","created":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T15:34:10Z","timestamp":1627054450000},"page":"2863-2878","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":38,"title":["Mantle cell lymphoma polarizes tumor-associated macrophages into M2-like macrophages, which in turn promote tumorigenesis"],"prefix":"10.1182","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1714-2377","authenticated-orcid":false,"given":"Kang","family":"Le","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular 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and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1428-8765","authenticated-orcid":false,"given":"Mitchell R.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine and Health Sciences, George Washington University, GW Cancer Center, Washington, DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2081-3941","authenticated-orcid":false,"given":"Mamta","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2021,7,23]]},"reference":[{"issue":"6","key":"2021072315340575000_B1","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/s41408-019-0209-5","article-title":"Patterns of survival in patients with recurrent mantle cell lymphoma in the modern era: progressive 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