ArticleJournal of immunology (Baltimore, Md. : 1950)2021
Leptin Augments Antitumor Immunity in Obesity by Repolarizing Tumor-Associated Macrophages.
Article in Journal of immunology (Baltimore, Md. : 1950), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 37 citations in OpenAlex.
- Trial
- Immune checkpoints and immunoregulation in metabolic diseases and cancers: pathological mechanisms and therapeutic potential.Signal transduction and targeted therapy · 2026Review
- Body Mass Index and Body Fat Percentage Are Associated with Clinical Outcomes in Patients Receiving PD-1/PD-L1 Inhibitors: A Prospective Exploratory Study.Journal of personalized medicine · 2026Article
- Remodeling the Immune Landscape: How Obesity-Induced SASPs Create a Pro-Tumorigenic Niche.Current obesity reports · 2026Review
- Leptin Signaling at the Crossroads of Obesity, Immunity, and Cancer: Mechanistic Insights and Therapeutic Implications.Biomolecules & therapeutics · 2026Review
- Identification of macrophage polarization-related genes for esophageal cancer risk: a multi-omics Mendelian randomization analysis.Clinical epigenetics · 2026Article
- Inflammatory Memory of Adipose Tissue Macrophages: From CD68 Footprint to Cardiometabolic and Cancer Risk During Weight Cycling.International journal of molecular sciences · 2026Review
- Impact of body mass index on progression-free survival and endocrine immune-related adverse events in advanced NSCLC patients treated with nivolumab: A retrospective cohort study.Northern clinics of Istanbul · 2026Article
- Obesity-induced metabolic reprogramming of the tumor immune microenvironment: mechanisms, spatial niches, and immunotherapy response.Frontiers in immunology · 2026Review
- Emerging Predictive Biomarkers of Immunotherapy Sensitivity in Patients with Non-Small Cell Lung Cancer.ImmunoTargets and therapy · 2026Review
- Leptin as a Potential Modifier of Neuroinflammation: Contrasting Roles in Alzheimer's Disease and Multiple Sclerosis.International journal of molecular sciences · 2025Review
- Host-related Determinants of Response to Immunotherapy in Non-small Cell Lung Cancer: The Interplay of Body Composition, Metabolism, Sex and Immune Regulation.Current oncology reports · 2025Review
- Murine Models of Obesity-Related Cancer Risk.Cancer prevention research (Philadelphia, Pa.) · 2025Review
- Estrogens determine the efficacy of cancer immunotherapy in obese males with melanoma.JCI insight · 2025Article
- Decoding resistance to immune checkpoint inhibitors in non-small cell lung cancer: a comprehensive analysis of plasma proteomics and therapeutic implications.Journal for immunotherapy of cancer · 2025Article
- Impact of body composition on pathological response to neoadjuvant immunotherapy in dMMR/MSI-H colorectal cancer.Frontiers in immunology · 2025Article
- The acid-sensing receptor GPR65 on tumor macrophages drives tumor growth in obesity.Science immunology · 2024Article
- Article
- Article
- Engineered Tumor-Immune Microenvironment On A Chip to Study T Cell-Macrophage Interaction in Breast Cancer Progression.Advanced healthcare materials · 2024Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Although obesity can promote cancer, it may also increase immunotherapy efficacy in what has been termed the obesity-immunotherapy paradox. Mechanisms of this effect are unclear, although obesity alters key inflammatory cytokines and can promote an inflammatory state that may modify tumor-infiltrating lymphocytes and tumor-associated macrophage populations. To identify mechanisms by which obesity affects antitumor immunity, we examined changes in cell populations and the role of the proinflammatory adipokine leptin in immunotherapy. Single-cell RNAseq demonstrated that obesity decreased tumor-infiltrating lymphocyte frequencies, and flow cytometry confirmed altered macrophage phenotypes with lower expression of inducible NO synthase and MHC class II in tumors of obese animals. When treated with anti-programmed cell death protein 1 (PD-1) Abs, however, obese mice had a greater absolute decrease in tumor burden than lean mice and a repolarization of the macrophages to inflammatory M1-like phenotypes. Mechanistically, leptin is a proinflammatory adipokine that is induced in obesity and may mediate enhanced antitumor immunity in obesity. To directly test the effect of leptin on tumor growth and antitumor immunity, we treated lean mice with leptin and observed tumors over time. Treatment with leptin, acute or chronic, was sufficient to enhance antitumor efficacy similar to anti-PD-1 checkpoint therapy. Further, leptin and anti-PD-1 cotreatment may enhance antitumor effects consistent with an increase in M1-like tumor-associated macrophage frequency compared with non-leptin-treated mice. These data demonstrate that obesity has dual effects in cancer through promotion of tumor growth while simultaneously enhancing antitumor immunity through leptin-mediated macrophage reprogramming.
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