ArticlePharmacological research2024
Decoupling FcRn and tumor contributions to elevated immune checkpoint inhibitor clearance in cancer cachexia.
Article in Pharmacological research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 10 citations in OpenAlex.
- Fruquintinib plus sintilimab in previously bevacizumab-treated, pMMR/MSS refractory metastatic colorectal cancer: a phase 2 clinical trial.Cancer immunology, immunotherapy : CII · 2025Trial
- Randomized Phase II Study of Nab-Paclitaxel and Gemcitabine With or Without Tocilizumab as First-Line Treatment in Advanced Pancreatic Cancer: Survival and Cachexia.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- Serum albumin is associated with immune-related hypothyroidism and treatment continuity in non-small cell lung cancer.International journal of clinical oncology · 2026Article
- Albumin Levels Are Predictive of Cachexia-Induced Time-Dependent Clearance of Therapeutic Antibodies: A Physiologically Based Pharmacokinetic Model of Durvalumab.CPT: pharmacometrics & systems pharmacology · 2026Article
- Fc gamma receptor binding modulates IgG clearance in cancer cachexia.Frontiers in immunology · 2026Article
- Optimizing Anti-PD1 Immunotherapy: An Overview of Pharmacokinetics, Biomarkers, and Therapeutic Drug Monitoring.Cancers · 2025Review
- Tumor intrinsic properties dictate Fc receptor expression and cancer cachexia associated increase in checkpoint inhibitor clearance.Frontiers in immunology · 2025Article
- Construction and validation of deep learning model for cachexia in extensive-stage small cell lung cancer patients treated with immune checkpoint inhibitors: a multicenter study.Translational lung cancer research · 2024Article
- Article
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Authors and funding
21 authors at 4 institutions in 2 countries.
Funding
Abstract
High baseline clearance of immune checkpoint inhibitors (ICIs), independent of dose or systemic exposure, is associated with cachexia and poor outcomes in cancer patients. Mechanisms linking ICI clearance, cachexia and ICI therapy failure are unknown. Here, we evaluate in four murine models and across multiple antibodies whether altered baseline catabolic clearance of administered antibody requires a tumor and/or cachexia and whether medical reversal of cachexia phenotype can alleviate altered clearance. Key findings include mild cachexia phenotype and lack of elevated pembrolizumab clearance in the MC38 tumor-bearing model. We also observed severe cachexia and decreased, instead of increased, baseline pembrolizumab clearance in the tumor-free cisplatin-induced cachexia model. Liver Fcgrt expression correlated with altered baseline catabolic clearance, though elevated clearance was still observed with antibodies having no (human IgA) or reduced (human H310Q IgG1) FcRn binding. We conclude cachexia phenotype coincides with altered antibody clearance, though tumor presence is neither sufficient nor necessary for altered clearance in immunocompetent mice. Magnitude and direction of clearance alteration correlated with hepatic Fcgrt, suggesting changes in FcRn expression and/or recycling function may be partially responsible, though factors beyond FcRn also contribute to altered clearance in cachexia.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.