ArticleJournal for immunotherapy of cancer2025
Pan-tumor analysis to investigate the obesity paradox in immune checkpoint blockade.
Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Radiotherapy-induced abscopal effects in immune checkpoint inhibitor-refractory metastatic disease: results from a large multicenter real-world cohort study.Oncoimmunology · 2026Article
- Overweight BMI compromises survival and correlates with aggressive phenotypes in early-onset but not late-onset rectal cancer patients.The oncologist · 2026Article
- Obesity Promotes Lung Carcinogenesis Through Airway Immune Dysfunction.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Article
- Obesity-derived metabolites modulate anti-tumor immunity in the tumor microenvironment: from mechanisms to clinical applications.BMC medicine · 2026Review
- Time-of-day of first checkpoint inhibitor dose influences clinical outcomes and immune responses in hepatocellular carcinoma.Journal for immunotherapy of cancer · 2026Article
- Exploring the role of metabolic disorders and gut microbiome in immune checkpoint regulation in cancer: PI3K/AKT/mTOR focus.Journal of physiology and biochemistry · 2026Review
- Clinically interpretable nomogram combining body composition and clinicopathological features for one year survival prediction in advanced solid tumors.Scientific reports · 2026Article
- Obesity and melanoma: unraveling the paradoxical survival benefit in immunotherapy.Cancer metastasis reviews · 2026Review
- Real-world effectiveness of first-line immunotherapy with or without chemotherapy versus chemotherapy alone in advanced non-small cell lung cancer.Frontiers in immunology · 2026Article
- The impact of excess weight and body fat on clinical outcomes of immune checkpoint inhibitors according to gender.Journal of endocrinological investigation · 2026Article
- Body mass index-defined overweight (but not obese) correlates with better postoperative prognosis in colorectal cancer.Journal of gastrointestinal oncology · 2025Article
- Immune Activation Signatures Associated with Fatigue in Cancer Patients Undergoing Immune Checkpoint Inhibitor Therapy.Cancer research communications · 2025Article
- From Bench to Bedside: Emerging Paradigms in CAR-T Cell Therapy for Solid Malignancies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- SensRORing cholesterol to drive protumoral myelopoiesis.Molecular oncology · 2025Article
- Pre-treatment endocrine-nutritional signatures predict clinical benefit from PD-1/PD-L1 blockade in hematologic malignancies.Frontiers in nutrition · 2025Review
- Nutritional status, immunonutrition, and gut microbiome: a coming of age for immunotherapy?Frontiers in immunology · 2025Review
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Abstract
backgroundObesity is a risk factor for developing cancer but is also associated with improved outcomes after treatment with immune checkpoint inhibitors (ICIs), a phenomenon called the obesity paradox. To interrogate mechanisms of divergent immune responses in obese and non-obese patients, we examined the relationship among obesity status, clinical responses, and immune profiles from a diverse, pan-tumor cohort of patients treated with ICI-based therapy.
methodsFrom June 2021 to March 2023, we prospectively collected serial peripheral blood samples from patients with advanced or metastatic solid tumors who received ICI as standard of care at Johns Hopkins. Patients were stratified by obesity status at treatment initiation, with obesity defined as body mass index (BMI)≥30 at treatment initiation and BMI≥18.5 and <30 considered non-obese; underweight patients (BMI<18.5) were excluded. We evaluated the concentration of 37 cytokines and used cytometry by time of flight to characterize immune cell clusters and cell-surface expression markers at baseline and on-treatment.
resultsWe enrolled 94 patients, of whom 30 (32%) were obese and 64 (68%) were non-obese. Compared with non-obese patients, obese patients had superior progression-free survival (HR: 0.44 (95% CI: 0.24 to 0.81), p=0.01) and overall survival (OS) (HR: 0.24 (95% CI: 0.07 to 0.80), p=0.02). Obese patients had lower serum IL-15 levels at treatment baseline and lower on-treatment levels of IL-6, IL-8, and IL-15. Low on-treatment IL-6 was associated with improved OS (HR: 0.27 (95% CI: 0.08 to 0.88), p=0.03), as was low on-treatment IL-8 (HR: 0.19 (95% CI: 0.05 to 0.70), p=0.01). Obese patients demonstrated lower levels of T effector cells with reduced expression of cytotoxicity markers and higher expression of exhaustion markers at baseline and on-treatment.
conclusionsObese and non-obese patients with cancer have divergent immunological responses to ICIs. Obesity is associated with reduced levels of certain inhibitory cytokines and higher expression of T-cell exhaustion markers. ICI-based therapy may more effectively reverse T-cell dysfunction in obese patients, potentially contributing to the paradoxically improved responses in this population.
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