ArticleEMBO molecular medicine2022
Carfilzomib modulates tumor microenvironment to potentiate immune checkpoint therapy for cancer.
Article in EMBO molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 56 citations in OpenAlex.
- Antibody-lectin chimeras for glyco-immune checkpoint blockade.Nature biotechnology · 2026Article
- Liposome-Encapsulated Carfilzomib as a Radiosensitizer in Solid Tumors.Molecular pharmaceutics · 2026Article
- Targeting the Dynamics Between TAMs and CAR-T Cells in Solid Tumor Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Enhancing immunotherapy efficacy in multiple myeloma and chronic lymphocytic leukemia: from combinatorial therapeutic approaches to gut microbiota modulation.Frontiers in immunology · 2026Review
- High-Throughput Heterospheroid-Based Screening Identifies Drugs That Reprogram Tumor-Associated Macrophages.Journal of immunology research · 2026Article
- C1QBP Drives M2 Macrophage Polarization Via TRAF2-CCL2 to Promote Oral Squamous Cell Carcinoma Progression.International dental journal · 2025Article
- Cancer targeting carfilzomib nanomedicine: a comprehensive review of delivery vehicles and efficacy.Nanomedicine (London, England) · 2025Review
- Article
- Targeting proteostasis for cancer therapy: current advances, challenges, and future perspectives.Molecular cancer · 2025Review
- FGF15/FGFR4 signaling suppresses M1 macrophage polarization and multi-organ inflammation in septic mice by inhibiting H3K18 lactylation-driven Irf7 expression through NF2-Hippo activation.Cell death & disease · 2025Article
- Integrating multi-omics data to optimize immunotherapy in endometrial cancer: a comprehensive study.Discover oncology · 2025Article
- [Research and Therapeutic Advances of 26S Proteasome Subunit in Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Review
- Targeted Delivery of c(RGDfk)-Modified Liposomes to Bone Marrow Through In Vivo Hitchhiking Neutrophils for Multiple Myeloma Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Maraviroc enhances Bortezomib sensitivity in multiple myeloma by inhibiting M2 macrophage polarization via PI3K/AKT/RhoA signaling pathway in macrophages.Cell division · 2025Article
- Immunocytes in the tumor microenvironment: recent updates and interconnections.Frontiers in immunology · 2025Review
- The role of macrophages in liver metastasis: mechanisms and therapeutic prospects.Frontiers in immunology · 2025Review
- Modulating and Imaging Macrophage Reprogramming for Cancer Immunotherapy.Phenomics (Cham, Switzerland) · 2024Review
- Mouse Models to Evaluate the Functional Role of the Tumor Microenvironment in Cancer Progression and Therapy Responses.Cold Spring Harbor perspectives in medicine · 2024Review
- Preclinical efficacy of carfilzomib in BRAF-mutant colorectal cancer models.Molecular oncology · 2024Article
- Evolving insights into the improvement of adoptive T-cell immunotherapy through PD-1/PD-L1 blockade in the clinical spectrum of lung cancer.Molecular cancer · 2024Review
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Impressive clinical benefit is seen in clinic with PD-1 inhibitors on portion of cancer patients. Yet, there remains an urgent need to develop effective synergizers to expand their clinical application. Tumor-associated macrophage (TAM), a type of M2-polarized macrophage, eliminates or suppresses T-cell-mediated anti-tumor responses. Transforming TAMs into M1 macrophages is an attractive strategy of anti-tumor therapy. Here, we conducted a high-throughput screening and found that Carfilzomib potently drove M2 macrophages to express M1 cytokines, phagocytose tumor cells, and present antigens to T cells. Mechanistically, Carfilzomib elicited unfolded protein response (UPR), activated IRE1α to recruit TRAF2, and activated NF-κB to transcribe genes encoding M1 markers in M2 macrophages. In vivo, Carfilzomib effectively rewired tumor microenvironment through reprogramming TAMs into M1-like macrophages and shrank autochthonous lung cancers in transgenic mouse model. More importantly, Carfilzomib synergized with PD-1 antibody to almost completely regress autochthonous lung cancers. Given the safety profiles of Carfilzomib in clinic, our work suggested a potentially immediate application of combinational treatment with Carfilzomib and PD-1 inhibitors for patients with solid tumors.
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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.