ArticleJournal for immunotherapy of cancer2022
PD-L1 blockade restores CAR T cell activity through IFN-γ-regulation of CD163+ M2 macrophages.
Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
88 citing papers in PubMed, 2 syntheses or guidelines pooled it, 103 citations in OpenAlex.
- Strategies and mechanisms for the enhancement of chimeric antigen receptor T-cell functions.Science China. Life sciences · 2026Pooled it
- Efficacy, safety, and PD-L1-defined outcomes of neoadjuvant immune checkpoint inhibitors in early-stage triple-negative breast cancer: a systematic review and meta-analysis.Frontiers in immunology · 2026Pooled it
- A phase 2 study of axicabtagene ciloleucel in relapsed or refractory large B-cell lymphoma in Japan: 1-year follow-up and biomarker analysis.International journal of hematology · 2023Trial
- Preclinical advances and mechanistic insights of CAR-T therapy for acute myeloid leukemia: from target iteration to microenvironment regulation.Annals of medicine · 2026Review
- Review
- Drug-associated cytokine release syndrome: a FAERS pharmacovigilance study with complementary transcriptomic analysis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Advances in cancer immunotherapy: adoptive cell therapy and immune cell engagers in solid tumours.British journal of cancer · 2026Review
- IL-12-engineered human PSMA-CAR T cells for the treatment of advanced prostate cancer.Molecular therapy. Advances · 2026Article
- The Conflicting Role of Myeloid Cells in CAR T-Cell Therapy.Cancer research · 2026Review
- Folate receptor beta targeting of tumor-associated macrophages improves lymphoma cell responses to CD19 CAR T cells.HemaSphere · 2026Article
- Gasdermin D antagonizes immunosuppression in prostate cancer by inducing LAMC2 degradation to block M2 macrophage polarization.Journal for immunotherapy of cancer · 2026Article
- Nanomaterials targeting cancer-associated fibroblasts to overcome stromal barriers in cancer immunotherapy.Journal of nanobiotechnology · 2026Review
- Programmed Cell Death Protein 1-Interleukin-2 Bispecific Agents for Cancer Therapy.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Mathematical modeling of immune counter-regulation predicts efficacy of fractionated CD8Scientific reports · 2026Article
- Determinants of Chimeric Antigen Receptor (CAR) T Cell Success: In Vitro and In Vivo Preclinical Assessment.Cancers · 2026Review
- Prognostic and Predictive Value of CD163+ Macrophages for Neoadjuvant Chemotherapy in Osteosarcoma.Biomedicines · 2026Article
- IGFBP2 promotes immunosuppression by regulating macrophage PD-L1 expression in NEUROD1-high small cell lung cancer.Journal of translational medicine · 2026Article
- Solid tumour CAR-T cells engineered with fusion proteins targeting PD-L1 for localized IL-12 delivery.Nature biomedical engineering · 2026Article
- Mechanisms of chemoresistance in diffuse large B‑cell lymphoma and novel therapeutic strategies (Review).International journal of oncology · 2026Review
- Cytokine-Engineered Chimeric Antigen Receptor-T Cell Therapy: How to Balance the Efficacy and Toxicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundThe immune suppressive tumor microenvironment (TME) that inhibits T cell infiltration, survival, and antitumor activity has posed a major challenge for developing effective immunotherapies for solid tumors. Chimeric antigen receptor (CAR)-engineered T cell therapy has shown unprecedented clinical response in treating patients with hematological malignancies, and intense investigation is underway to achieve similar responses with solid tumors. Immunologically cold tumors, including prostate cancers, are often infiltrated with abundant tumor-associated macrophages (TAMs), and infiltration of CD163
methodsTo model this in vitro, we utilized a novel co-culture system with tumor cells, CAR T cells, and polarized M1 or M2 macrophages from CD14
resultsWe observed inhibition of CAR T cell activity with the presence of M2 macrophages, but not M1 macrophages, coinciding with a robust induction of programmed death ligand-1 (PD-L1) in M2 macrophages. We observed similar PD-L1 expression in TAMs following CAR T cell therapy in the TME of humanized mice. PD-L1, but not programmed cell death protein-1, blockade in combination with CAR T cell therapy altered phenotypes to more M1-like subsets and led to loss of CD163
conclusionThis study reveals an alternative mechanism by which the combination of CAR T cells and immune checkpoint blockade modulates the immune landscape of solid tumors to enhance therapeutic efficacy of CAR T cells.
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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.