ArticleThe Journal of clinical investigation2021
Inhibition of estrogen signaling in myeloid cells increases tumor immunity in melanoma.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 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
88 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.
- PD-1/PD-L1 immune checkpoint blockade in breast cancer: research insights and sensitization strategies.Molecular cancer · 2024Pooled it
- Multipeptide vaccines for melanoma in the adjuvant setting: long-term survival outcomes and post-hoc analysis of a randomized phase II trial.Nature communications · 2024Trial
- PD-L1 blockade in combination with carboplatin as immune induction in metastatic lobular breast cancer: the GELATO trial.Nature cancer · 2023Trial
- Selective estrogen receptor degraders and their effect on the breast cancer immune microenvironment.The Journal of clinical investigation · 2026Review
- Pregnancy-Associated Melanoma: A Molecular Reappraisal of the Hormonal Hypothesis, Illustrated by a Postpartum-Persistent Melanoma In Situ.Diagnostics (Basel, Switzerland) · 2026Article
- Pulmonary alveolar proteinosis diagnosed during leuprorelin acetate therapy for ovarian endometrioma: a case report.BMC pulmonary medicine · 2026Article
- Association between cumulative lifetime exposure to reproductive hormones and tumor-infiltrating lymphocytes, CD4 +, and CD8 + T cells among women with breast cancer.Cancer immunology, immunotherapy : CII · 2026Article
- Body Composition and Melanoma Outcomes in Patients on Immunotherapy or Targeted Therapy: An Analysis from Canadian Melanoma Research Network.Current oncology (Toronto, Ont.) · 2026Article
- Sex differences in non-reproductive cancers: mechanistic roles of sex-hormone signaling.Cell communication and signaling : CCS · 2026Review
- Clinicopathological Factors Influencing PD-L1 Expression and the Effect of Immune Checkpoint Inhibitors on Survival Outcomes in Patients with Gastric Cancer Depending on Sex in a Tertiary Hospital in South Korea.Cancer research and treatment · 2026Article
- GABA signaling activation drives glioblastoma progression in female mice through myeloid-derived suppressor cells.Nature cancer · 2026Article
- A pan-cancer single-cell atlas uncovers the role of sex hormones and chromosomes in sex-divergent reprogramming of the tumor microenvironment.Cell communication and signaling : CCS · 2026Article
- Article
- Proteogenomic decoding of chemotherapy resistance in patients with triple-negative breast cancer.Genome biology · 2026Article
- Sex Differences in Cancer Immunotherapy-Clinical Evidence and Mechanisms With a Focus on NSCLC.Immunological reviews · 2026Review
- Sexual dimorphism in cancer: molecular mechanisms and precision oncology perspectives.Biology of sex differences · 2026Review
- Estrogen receptor α expression in tumor-infiltrating lymphocytes from patients with endometrial cancer.Oncology letters · 2026Article
- Estrogen receptor signaling drives immune evasion and immunotherapy resistance in HR+ breast cancer.The Journal of clinical investigation · 2026Article
- scXDR: drug response prediction across single-cell datasets via heterogeneous network transfer learning.Communications biology · 2026Article
- Recent Advances (2020-2025) in Estrogen and ER-Positive Breast Cancer: Receptor Signaling, Tumor Microenvironment, Endocrine Therapy Resistance and Innovative Treatment Strategies-A Comprehensive Review.Cancer management and research · 2026Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
18 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune checkpoint blockade (ICB) therapies have significantly prolonged patient survival across multiple tumor types, particularly in melanoma. Interestingly, sex-specific differences in response to ICB have been observed, with males receiving a greater benefit from ICB than females, although the mechanism or mechanisms underlying this difference are unknown. Mining published transcriptomic data sets, we determined that the response to ICBs is influenced by the functionality of intratumoral macrophages. This puts into context our observation that estrogens (E2) working through the estrogen receptor α (ERα) stimulated melanoma growth in murine models by skewing macrophage polarization toward an immune-suppressive state that promoted CD8+ T cell dysfunction and exhaustion and ICB resistance. This activity was not evident in mice harboring macrophage-specific depletion of ERα, confirming a direct role for estrogen signaling within myeloid cells in establishing an immunosuppressed state. Inhibition of ERα using fulvestrant, a selective estrogen receptor downregulator (SERD), decreased tumor growth, stimulated adaptive immunity, and increased the antitumor efficacy of ICBs. Further, a gene signature that determines ER activity in macrophages predicted survival in patients with melanoma treated with ICB. These results highlight the importance of E2/ER signaling as a regulator of intratumoral macrophage polarization, an activity that can be therapeutically targeted to reverse immune suppression and increase ICB efficacy.
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.