ArticleBritish journal of cancer2006
Monocytes and neutrophils as 'bad guys' for the outcome of interleukin-2 with and without histamine in metastatic renal cell carcinoma--results from a randomised phase II trial.
Article in British journal of cancer, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Immunotherapy for metastatic renal cell carcinoma.The Cochrane database of systematic reviews · 2017Pooled it
- Surrogacy of tumor response and progression-free survival for overall survival in metastatic breast cancer resistant to both anthracyclines and taxanes.International journal of clinical oncology · 2011Trial
- The role of reactive oxygen species in the transformation from prostatitis to prostate cancer: a review.Frontiers in immunology · 2025Review
- Systemic inflammation in older patients with breast cancer: the missing point in geriatric evaluations to sharpen survival prediction.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Article
- Macrophage Phenotype in Combination with Tumor Microbiome Composition Predicts RCC Patients' Survival: A Pilot Study.Biomedicines · 2022Article
- Reprogramming NK cells and macrophages via combined antibody and cytokine therapy primes tumors for elimination by checkpoint blockade.Cell reports · 2021Article
- Histamine in cancer immunology and immunotherapy. Current status and new perspectives.Pharmacology research & perspectives · 2021Review
- Metabolic regulatory crosstalk between tumor microenvironment and tumor-associated macrophages.Theranostics · 2021Review
- Systemic Inflammation Response Index is an Independent Prognostic Indicator for Patients with Renal Cell Carcinoma Undergoing Laparoscopic Nephrectomy: A Multi-Institutional Cohort Study.Cancer management and research · 2021Article
- NOX2-Derived Reactive Oxygen Species in Cancer.Oxidative medicine and cellular longevity · 2020Review
- Peripheral blood biomarkers correlate with outcomes in advanced non-small cell lung Cancer patients treated with anti-PD-1 antibodies.Journal for immunotherapy of cancer · 2018Article
- Redox control of cancer cell destruction.Redox biology · 2018Review
- Preoperative Lymphocyte-Monocyte Ratio Ameliorates the Accuracy of Differential Diagnosis in Non-Metastatic Infiltrative Renal Masses.Yonsei medical journal · 2017Article
- Review
- Emerging role of tumor-associated macrophages as therapeutic targets in patients with metastatic renal cell carcinoma.Cancer immunology, immunotherapy : CII · 2013Review
- Modulation of neutrophil oxidative burst via histamine receptors.British journal of pharmacology · 2013Review
- Tumour-associated CD66b+ neutrophil count is an independent prognostic factor for recurrence in localised cervical cancer.British journal of cancer · 2013Article
- Histamine: an undercover agent in multiple rare diseases?Journal of cellular and molecular medicine · 2012Review
- Apoptosis, angiogenesis, inflammation, and oxidative stress: basic interactions in patients with early and metastatic breast cancer.Journal of cancer research and clinical oncology · 2012Article
- Antitumor properties of histamine in vivo.Nature medicine · 2011Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Histamine (HDC) inhibits formation and release of phagocyte-derived reactive oxygen species, and thereby protects natural killer (NK) and T cells against oxidative damage. Thus, the addition of histamine may potentially improve the efficacy of interleukin-2 (IL-2). We have explored this potential mechanism clinically in two randomised phase II trials in metastatic renal cell carcinoma (mRCC). In parallel with the clinical trial in Denmark (n=63), we obtained serial blood samples and tumour biopsies searching for a potential histamine effect in situ. At baseline and on-treatment weeks 3 and 8, we monitored the 'good guys' (i.e. NK and T cells) and 'bad guys' (i.e. monocytes/macrophages and neutrophils) simultaneously in blood (n=59) and tumour tissue (n=44). Patients with high number of monocytes and neutrophils in peripheral blood had very poor survival, with apparently no benefit from either IL-2 alone or IL-2/HDC treatment. Blood monocytes (r=-0.36, P=0.01) and neutrophils (r=-0.46, P=0.001) were negatively correlated with cytotoxicity, whereas blood NK cells were positively correlated with cytotoxicity (r=0.39, P=0.002). Treatment with IL-2 alone resulted in a significantly higher number of circulating monocytes (P=0.037) and intratumoral macrophages (P=0.005) compared with baseline. In contrast, IL-2/HDC resulted in an unchanged number of circulating monocytes and intratumoral macrophages, and in addition, a significantly increased number of intratumoral CD56(+) NK cells (P=0.008) and CD8(+) T cells (P=0.019) compared with baseline. The study provides evidence that circulating monocytes and neutrophils are powerful negative prognostic factors for IL-2-based immunotherapy and establishes a biological rationale for the potential use of histamine in conjunction with IL-2 in mRCC.
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