{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T13:34:52Z","timestamp":1791466492588,"version":"4.3.4"},"reference-count":42,"publisher":"American Society of Hematology","issue":"18","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,5,2]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>Rituximab (RTX) and other monoclonal antibodies (mAbs) that bind directly to malignant cells are of great clinical value but are not effective for all patients. A major mechanism of action of RTX is antibody-dependent cellular cytotoxicity (ADCC) mediated by natural killer (NK) cells. Prior in\u00a0vitro studies in our laboratory demonstrated that T cells contribute to maintaining the viability and cytotoxic potential of NK cells activated by anti-CD20\u2013coated target B cells. Here, we conducted studies using a novel mouse model and clinical correlative analysis to assess whether T-cell help contribute to RTX-mediated NK-cell ADCC in the tumor microenvironment (TME) in\u00a0vivo. A humanized mouse model was developed using Raji lymphoma cells and normal donor peripheral blood mononuclear cells that allows for control of T-cell numbers in the lymphoma TME. In this model, NK-cell viability and CD16 and CD25 expression dropped after RTX in the absence of T cells but increased in the presence of T cells. RTX therapy was more effective when T cells were present and was ineffective when NK cells were depleted. In patients with indolent lymphoma, fine needle aspirates were obtained before and \u223c1 week after treatment with a RTX-containing regimen. There was a strong correlation between CD4+ T\u00a0cells as well as total T cells in the pretherapy TME and an increase in NK-cell CD16 and CD25 expression after RTX. We conclude that T-cell help in the TME enhances RTX-mediated NK-cell viability and ADCC.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2023023370","type":"journal-article","created":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T17:59:52Z","timestamp":1709920792000},"page":"1816-1824","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":28,"title":["T-cell help in the tumor microenvironment enhances rituximab-mediated NK-cell ADCC"],"prefix":"10.1182","volume":"143","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3071-8887","authenticated-orcid":false,"given":"Jyoti","family":"Arora","sequence":"first","affiliation":[{"name":"1Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA"},{"name":"2Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6451-7795","authenticated-orcid":false,"given":"Sabarish","family":"Ayyappan","sequence":"additional","affiliation":[{"name":"1Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA"},{"name":"3Department of Internal Medicine, University of Iowa, Iowa City, IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1552-6171","authenticated-orcid":false,"given":"Chaobo","family":"Yin","sequence":"additional","affiliation":[{"name":"1Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1250-1710","authenticated-orcid":false,"given":"Brian J.","family":"Smith","sequence":"additional","affiliation":[{"name":"1Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA"},{"name":"4Department of Biostatistics, University of Iowa, Iowa City, IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3769-7247","authenticated-orcid":false,"given":"Caitlin D.","family":"Lemke-Miltner","sequence":"additional","affiliation":[{"name":"1Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8308-5297","authenticated-orcid":false,"given":"Zhaoming","family":"Wang","sequence":"additional","affiliation":[{"name":"1Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7891-9891","authenticated-orcid":false,"given":"Umar","family":"Farooq","sequence":"additional","affiliation":[{"name":"1Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA"},{"name":"3Department of Internal Medicine, University of Iowa, Iowa City, 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