{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:08:24Z","timestamp":1788948504413,"version":"build-2803163510"},"reference-count":102,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH NCI","doi-asserted-by":"publisher","award":["1R01CA286117-01"],"award-info":[{"award-number":["1R01CA286117-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH NCI","doi-asserted-by":"publisher","award":["P30CA016058"],"award-info":[{"award-number":["P30CA016058"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"OSU Division of Hematology Sponsored Research Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Toll-like receptors (TLRs) are crucial for eliciting immune responses against pathogens such as bacteria and viruses. TLR activation has also been studied for its potential to drive antitumor activity in immune cells. TLR8 is an intracellular receptor that recognizes single-stranded RNA and promotes antiviral responses, including the release of cytokines such as TNF\u03b1 and type I IFN. Previously we have shown that TLR8 activation can also modulate the expression of Fc\u03b3 receptors (Fc\u03b3R), which are major drivers of antibody-mediated tumor cell clearance. Hence, TLR8 agonist treatment represents a potential means of overcoming tumor-related immunosuppression and enhancing the efficacy of antibody therapy. In chronic lymphocytic leukemia, the use of therapeutic antibodies against CD20 has become standard for treatment. However, the immune effector cells show suppressed phenotypes and weakened responses compared to their healthy-donor counterparts. Here, we investigated TLR8 agonist treatment as a means to overcome this immune suppression and enhance cellular antibody-mediated responses. Upon stimulation with the agonist TL8-506, primary CLL-patient monocytes showed an increase in the expression of activating Fc\u03b3R in conjunction with reduced expression of regulatory receptors. Cytokine production was also enhanced and there was a shift in phenotypic markers, suggesting the adoption of a more M1-like state. Treatment with TLR8 agonist also elicited production of IFN\u03b3 and Granzyme B and enhanced antibody-dependent cellular cytotoxicity of antibody-coated B cells by NK cells. Agonist treatment also increased the phagocytic activity of neutrophils but did not affect the formation of neutrophil extracellular traps (NETs). Taken together, these results suggest that TLR8 agonists may help counteract the suppressed phenotypes of immune effector cells and may enhance the efficacy of antibody therapy for CLL.<\/jats:p>","DOI":"10.3390\/ijms27188003","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T09:24:02Z","timestamp":1788945842000},"page":"8003","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TLR8 Stimulation Leads to Microenvironment Activation and Enhanced Antibody-Dependent Cellular Responses in CLL"],"prefix":"10.3390","volume":"27","author":[{"given":"Giovanna","family":"Merchand-Reyes","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Gauri","family":"Anyarambhatla","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Maria L.","family":"Valencia Pena","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renie","family":"Mensah-Bonsu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Ramasamy","family":"Santhanam","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Xiaokui","family":"Mo","sequence":"additional","affiliation":[{"name":"Center for Biostatistics, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"},{"name":"Department of Biomedical Informatics, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5583-9194","authenticated-orcid":false,"given":"Frank H.","family":"Robledo-Avila","sequence":"additional","affiliation":[{"name":"Center for Microbe and Immunity Research, Abigail Wexner Research Institute, Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susheela","family":"Tridandapani","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Jonathan P.","family":"Butchar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1002\/ajh.27546","article-title":"Chronic Lymphocytic Leukemia: 2025 Update on the Epidemiology, Pathogenesis, Diagnosis, and Therapy","volume":"100","author":"Hallek","year":"2025","journal-title":"Am. 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