ArticleThe Journal of clinical investigation2017
A CCR4 antagonist reverses the tumor-promoting microenvironment of renal cancer.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
55 citing papers in PubMed, 106 citations in OpenAlex.
- Mogamulizumab in Combination with Nivolumab in a Phase I/II Study of Patients with Locally Advanced or Metastatic Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Targeting BCL9/BCL9L enhances CD4Acta pharmacologica Sinica · 2026Article
- Chemokine-chemokine receptor axis: Emerging immunotherapeutic paradigms for solid tumor microenvironment reprogramming.Chinese medical journal · 2026Review
- Matrix structure and microenvironment dynamics correlate with chemotherapy response in ovarian cancer.iScience · 2026Article
- Article
- Article
- Angiogenic and immune predictors of neoadjuvant axitinib response in renal cell carcinoma with venous tumour thrombus.Nature communications · 2025Article
- Single‑cell transcriptomic analysis revealed the tumor‑associated microenvironment of papillary thyroid carcinoma with metastasis.Oncology letters · 2025Article
- Targeting cytokine and chemokine signaling pathways for cancer therapy.Signal transduction and targeted therapy · 2024Review
- High-dimensional mapping of human CEACAM1 expression on immune cells and association with melanoma drug resistance.Communications medicine · 2024Article
- Immunostimulatory effects of Toll-like receptor ligands as adjuvants in establishing a novel mouse model for pemphigus vulgaris.Clinical and translational medicine · 2024Article
- Small-molecule agents for cancer immunotherapy.Acta pharmaceutica Sinica. B · 2024Review
- Cancer Stem Cells and the Tumor Microenvironment in Tumor Drug Resistance.Stem cell reviews and reports · 2023Review
- Biomarkers for Immune Checkpoint Inhibitors in Renal Cell Carcinoma.Journal of clinical medicine · 2023Review
- CCR4 Blockade Diminishes Intratumoral Macrophage Recruitment and Augments Survival of Syngeneic Pancreatic Cancer-Bearing Mice.Biomedicines · 2023Article
- Efficient Redirection of NK Cells by Genetic Modification with Chemokine Receptors CCR4 and CCR2B.International journal of molecular sciences · 2023Article
- CXCL11-armed oncolytic adenoviruses enhance CAR-T cell therapeutic efficacy and reprogram tumor microenvironment in glioblastoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- CC Chemokine Receptor 4 (CCR4) as a Possible New Target for Therapy.International journal of molecular sciences · 2022Review
- Rethinking the chemokine cascade in brain metastasis: Preventive and therapeutic implications.Seminars in cancer biology · 2022Review
- Harnessing cytokines and chemokines for cancer therapy.Nature reviews. Clinical oncology · 2022Review
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
16 authors at 1 institution in 3 countries.
Funding
Abstract
Elevated expression of the chemokine receptor CCR4 in tumors is associated with poor prognosis in several cancers. Here, we have determined that CCR4 was highly expressed in human renal cell carcinoma (RCC) biopsies and observed abnormal levels of CCR4 ligands in RCC patient plasma. An antagonistic anti-CCR4 antibody had antitumor activity in the RENCA mouse model of RCC. CCR4 inhibition did not reduce the proportion of infiltrating leukocytes in the tumor microenvironment but altered the phenotype of myeloid cells, increased NK cell and Th1 cytokine levels, and reduced immature myeloid cell infiltrate and blood chemokine levels. In spite of prominent changes in the myeloid compartment, the anti-CCR4 antibody did not affect RENCA tumors in T cell-deficient mice, and treatment with an anti-class II MHC antibody abrogated its antitumor activity. We concluded that the effects of the anti-CCR4 antibody required the adaptive immune system and CD4+ T cells. Moreover, CCL17-induced IFN-γ production was reduced when Th1-polarized normal CD4+ T cells were exposed to the CCR4 ligand, evidencing the involvement of CCR4 in Th1/Th2 regulation. The anti-CCR4 antibody, alone or in combination with other immune modulators, is a potential treatment approach to human solid cancers with high levels of CCR4-expressing tumor-infiltrating leukocytes and abnormal plasma CCR4 ligand levels.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.