ArticleCancer discovery2023
p38MAPKα Stromal Reprogramming Sensitizes Metastatic Breast Cancer to Immunotherapy.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 17 citations in OpenAlex.
- MERTK inhibition cooperates with immunomodulatory cyclophosphamide to induce CXCL9⁺ monocyte-macrophage programming and durable antitumor immunity in triple negative breast cancer.Cancer immunology research · 2026Article
- Therapy as a State-Generator: Dynamic Phenotypic Landscapes and Adaptive Stress Circuits in Chemotherapy Resistance of Breast Cancer.Antioxidants (Basel, Switzerland) · 2026Review
- Targeting p38α in cancer: challenges, opportunities, and emerging strategies.Molecular oncology · 2026Review
- MERTK inhibition cooperates with immunomodulatory cyclophosphamide to induce CXCL9bioRxiv : the preprint server for biology · 2026Article
- Modulation of gut microbiota and its metabolite Equol by Huaier granule suppresses hepatocellular carcinoma via the gut-liver axis.NPJ biofilms and microbiomes · 2026Article
- Targeting the tripartite axis of immune-metabolic-spatial crosstalk to overcome therapy resistance in breast cancer.Frontiers in immunology · 2026Review
- Chemotherapy-induced adipo-lineage cell senescence drives bone loss.Nature communications · 2025Article
- p38 blockade reverses the immune suppressive tumor microenvironment in metastatic breast cancer.Research square · 2025Article
- Cellular senescence offers distinct immunological vulnerabilities in cancer.Trends in cancer · 2025Review
- First-in-class ultralong-target-residence-time p38α inhibitors as a mitosis-targeted therapy for colorectal cancer.Nature cancer · 2025Article
- Gram-Negative Microflora Dysbiosis Facilitates Tumor Progression and Immune Evasion by Activating the CCL3/CCL5-CCR1-MAPK-PD-L1 Pathway in Esophageal Squamous Cell Carcinoma.Molecular cancer research : MCR · 2025Article
- A Novel KIF4A-related Model for Predicting Immunotherapy Response and Prognosis in Kidney Renal Clear Cell Carcinoma.Combinatorial chemistry & high throughput screening · 2025Article
- Senescent CAFs Mediate Immunosuppression and Drive Breast Cancer Progression.Cancer discovery · 2024Article
- Long noncoding RNA Malat1 protects against osteoporosis and bone metastasis.Nature communications · 2024Article
- MiR-200c reprograms fibroblasts to recapitulate the phenotype of CAFs in breast cancer progression.Cell stress · 2024Article
- Advances in single-cell RNA sequencing and its applications in cancer research.Journal of hematology & oncology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
25 authors at 4 institutions in 1 country.
Funding
Abstract
Metastatic breast cancer is an intractable disease that responds poorly to immunotherapy. We show that p38MAPKα inhibition (p38i) limits tumor growth by reprogramming the metastatic tumor microenvironment in a CD4+ T cell-, IFNγ-, and macrophage-dependent manner. To identify targets that further increased p38i efficacy, we utilized a stromal labeling approach and single-cell RNA sequencing. Thus, we combined p38i and an OX40 agonist that synergistically reduced metastatic growth and increased overall survival. Intriguingly, patients with a p38i metastatic stromal signature had better overall survival that was further improved by the presence of an increased mutational load, leading us to ask if our approach would be effective in antigenic breast cancer. The combination of p38i, anti-OX40, and cytotoxic T-cell engagement cured mice of metastatic disease and produced long-term immunologic memory. Our findings demonstrate that a detailed understanding of the stromal compartment can be used to design effective antimetastatic therapies. SIGNIFICANCE: Immunotherapy is rarely effective in breast cancer. We dissected the metastatic tumor stroma, which revealed a novel therapeutic approach that targets the stromal p38MAPK pathway and creates an opportunity to unleash an immunologic response. Our work underscores the importance of understanding the tumor stromal compartment in therapeutic design. This article is highlighted in the In This Issue feature, p. 1275.
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.