{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:17:44Z","timestamp":1787026664904,"version":"build-2736575974"},"reference-count":85,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Patients with cancer-cachexia display a general resistance to Immune Checkpoint Inhibitor (ICI) therapy, as well as an elevated baseline catabolic clearance (CL) of ICIs, which serves as a prognostic indicator of overall survival independent of dose and drug exposure. Increased rate of ICI CL is present in the Lewis Lung Carcinoma (LLC) murine model of cachexia, but absent in the non-cachectic MC38 model. Fc-Gamma Receptors (Fc\u03b3Rs) bind the Fc portion of antibodies and can impact ICI anti-tumor efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A pharmacokinetic study of human IgG1 (hIgG1) and hIgG1 with D265A (D265A) mutation, to abrogate all Fc\u03b3R binding, was performed in mice that were either LLC tumor bearing (TB) or tumor free (TF). Immunofluorescence studies using fluorescence conjugated anti-human IgG were conducted to detect and localize infused hIgG1 in the mouse liver. To further investigate, Fc\u03b3RIIb knockout mice were utilized in pharmacokinetic studies with hIgG.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CL of both IgG1 and D265A significantly increased in LLC TB mice compared to TF controls, however the CL of D265A was significantly lower compared to hIgG1 in LLC TB mice. Immunofluorescence image of mouse livers portrays colocalization of the administered hIgG1 and Fc\u03b3RIIb in liver sinusoidal endothelial cells (LSEC), as well as upregulated hepatic expression of Fc\u03b3RIIb in LLC TB. However, hIgG1 CL was unaffected by whole body knockout of Fc\u03b3RIIb.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Reduced CL of D265A versus IgG1 in LLC TB mice, but not TF mice, suggests Fc\u03b3Rs are involved in catabolic CL of IgG antibodies in the presence of LLC tumors and cancer cachexia. This suggest that in the presence of LLC tumors, changes in Fc\u03b3R expression and\/or function lead to significantly altered antibody CL mediated by Fc\u03b3R. This apparent role of Fc\u03b3Rs in antibody catabolism cannot be solely explained by Fc\u03b3RIIb, but instead suggests the significance of other Fc\u03b3Rs in cachexia-associated increases in antibody CL.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1676732","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T05:34:38Z","timestamp":1774935278000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Fc gamma receptor binding modulates IgG clearance in cancer cachexia"],"prefix":"10.3389","volume":"17","author":[{"given":"Bryan C.","family":"Remaily","sequence":"first","affiliation":[{"name":"Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University","place":["Columbus, OH, United 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