ArticleJournal for immunotherapy of cancer2015
NK cells and CD8+ T cells cooperate to improve therapeutic responses in melanoma treated with interleukin-2 (IL-2) and CTLA-4 blockade.
Article in Journal for immunotherapy of cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Pooled it
- Talimogene Laherparepvec in Combination With Ipilimumab in Previously Untreated, Unresectable Stage IIIB-IV Melanoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2016Trial
- Article
- Targeting cytokine/chemokine signaling to convert immunologically cold tumors into hot: Emerging strategies in cancer immunotherapy.Acta pharmaceutica Sinica. B · 2026Review
- Downregulation of PDIA4 inhibits proliferation and migration in human oral squamous cell carcinoma.Hereditas · 2025Article
- Tumor microenvironments with an active type I IFN response are sensitive to inhibitors of heme degradation.JCI insight · 2025Article
- Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease.Signal transduction and targeted therapy · 2025Review
- AnScience immunology · 2025Article
- Regulation of NK cell development, maturation, and antitumor responses by the nuclear receptor NR2F6.Cell death & disease · 2025Article
- Engineered cytokine/antibody fusion proteins improve IL-2 delivery to pro-inflammatory cells and promote antitumor activity.JCI insight · 2024Article
- Toxicity in the era of immune checkpoint inhibitor therapy.Frontiers in immunology · 2024Review
- Attenuated Dengue virus PV001-DV induces oncolytic tumor cell death and potent immune responses.Journal of translational medicine · 2023Article
- Radiotherapy combined with immunotherapy could improve the immune infiltration of melanoma in mice and enhance the abscopal effect.Radiation oncology journal · 2023Article
- NK Cells in Cancer: Mechanisms of Dysfunction and Therapeutic Potential.International journal of molecular sciences · 2023Review
- Anticancer traits of chimeric antigen receptors (CARs)-Natural Killer (NK) cells as novel approaches for melanoma treatment.BMC cancer · 2022Article
- Immune cellular components and signaling pathways in the tumor microenvironment.Seminars in cancer biology · 2022Review
- Pivotal roles of tumor-draining lymph nodes in the abscopal effects from combined immunotherapy and radiotherapy.Cancer communications (London, England) · 2022Article
- Heptamethine Cyanine-Loaded Nanomaterials for Cancer Immuno-Photothermal/Photodynamic Therapy: A Review.Pharmaceutics · 2022Review
- Contribution of natural killer cells in innate immunity against colorectal cancer.Frontiers in oncology · 2022Review
- FLG Is a Potential Biomarker of Prognosis and Immunotherapy in Skin Cutaneous Melanoma.Applied bionics and biomechanics · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMelanoma is one of the few types of cancer with an increasing annual incidence. While a number of immunotherapies for melanoma have been associated with significant clinical benefit, including high-dose IL-2 and cytotoxic T lymphocyte antigen 4 (CTLA-4) blockade, clinical response to either of these single agents has been limited to 11-20% of treated patients. Therefore, in this study, we sought to test the hypothesis that the combination of IL-2 and CTLA-4 blockade could mediate a more profound therapeutic response.
methodsHere, B6 mice were challenged with poorly immunogenic B16 melanoma on day 0, and treated with CTLA-4 blocking antibody (100 μg/mouse) on days 3, 6, and 9, and IL-2 (100,000 units) twice daily on days 4-8, or both.
resultsA highly significant synergistic effect that delayed tumor growth and prolonged survival was demonstrated with the combination immunotherapy compared to either monotherapy alone. The therapeutic effect of combination immunotherapy was dependent on both CD8+ T and NK cells and co-depletion of these subsets (but not either one alone) abrogated the therapeutic effect. CTLA-4 blockade increased immune cell infiltration (including CD8+ T cells and NK cells) in the tumor and IL-2 reduced the proportion of highly differentiated/exhausted tumor-infiltrating NK cells.
conclusionsThese results have implications for the design of clinical trials in patients with metastatic melanoma and provide new insights into how the immune system may be mediating anti-tumor activity with combination IL-2 and CTLA-4 blockade in melanoma.
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.