ArticleProceedings of the National Academy of Sciences of the United States of America2018
Macrophages impede CD8 T cells from reaching tumor cells and limit the efficacy of anti-PD-1 treatment.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 589 papers.
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Who cites it
589 citing papers in PubMed.
- Tebentafusp, a T cell engager, promotes macrophage reprogramming and in combination with IL-2 overcomes macrophage immunosuppression in cancer.Nature communications · 2025Trial
- Neoadjuvant vidutolimod and nivolumab in high-risk resectable melanoma: A prospective phase II trial.Cancer cell · 2024Trial
- A gut microbiota rheostat forecasts responsiveness to PD-L1 and VEGF blockade in mesothelioma.Nature communications · 2024Trial
- Early Immune Remodeling Steers Clinical Response to First-Line Chemoimmunotherapy in Advanced Gastric Cancer.Cancer discovery · 2024Trial
- A bottleneck-first evaluation of antigen delivery platforms for therapeutic cancer vaccines.Materials today. Bio · 2026Review
- A Comparison of Mechanisms Driving Lesion Outcomes During Lung Tumor and Tuberculosis Granuloma Formation.Bulletin of mathematical biology · 2026Article
- XBP1 signaling from tumor metabolic stress to myeloid driven immunotherapy resistance (Review).International journal of molecular medicine · 2026Review
- Decoding spatiotemporal fibrotic and cellular immunosuppression of therapeutic T cells in live pancreatic ductal adenocarcinoma.Molecular systems biology · 2026Article
- The tumoural landscape of lymphocytes and immune pathways in immunotherapy-treated melanoma patients.Genes and immunity · 2026Article
- Spatial and Single-Cell Multi-Omics Analyses of T-Cell Subsets and Interactions in Melanoma Lymph Node Metastasis.Experimental dermatology · 2026Review
- Current status and challenges of TCR-T cell therapy for AML/MDS.International journal of hematology · 2026Review
- Immune-pressure redistribution in resistance to PD-1/PD-L1 blockade: mechanisms, biomarkers, and therapeutic design.Molecular cancer · 2026Review
- Next-generation macrophage engineering in cancer therapy: From TAM reprogramming to CAR-macrophages.Molecular therapy. Nucleic acids · 2026Review
- Reduced colony-stimulating factor 1 receptor expression in myeloid cells has limited impact on chronic lymphocytic leukaemia progression.British journal of haematology · 2026Article
- PGK1 Suppresses CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Macrophage Plasticity in Cancer Therapy: Function, Timing, and Tradeoffs.International journal of molecular sciences · 2026Review
- Identification of disulfidptosis-related molecular subtypes in pleural mesothelioma demonstrates a correlation with the immune infiltration, prognosis and therapy efficacy.Discover oncology · 2026Article
- Single-nucleus multimodal spatial transcriptomics reveals spatial colocalization of neoantigen-expressing tumor cells and cognate T cells.Nature biotechnology · 2026Article
- Association of tumor-infiltrating lymphocytes and proinflammatory biomarkers with breast cancer molecular subtypes: analysis of the MEND study.Breast cancer research and treatment · 2026Article
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Authors and funding
15 authors.
Funding
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Abstract
In a large proportion of cancer patients, CD8 T cells are excluded from the vicinity of cancer cells. The inability of CD8 T cells to reach tumor cells is considered an important mechanism of resistance to cancer immunotherapy. We show that, in human lung squamous-cell carcinomas, exclusion of CD8 T cells from tumor islets is correlated with a poor clinical outcome and with a low lymphocyte motility, as assessed by dynamic imaging on fresh tumor slices. In the tumor stroma, macrophages mediate lymphocyte trapping by forming long-lasting interactions with CD8 T cells. Using a mouse tumor model with well-defined stromal and tumor cell areas, macrophages were depleted with PLX3397, an inhibitor of colony-stimulating factor-1 receptor (CSF-1R). Our results reveal that a CSF-1R blockade enhances CD8 T cell migration and infiltration into tumor islets. Although this treatment alone has minor effects on tumor growth, its combination with anti-PD-1 therapy further increases the accumulation of CD8 T cells in close contact with malignant cells and delays tumor progression. These data suggest that the reduction of macrophage-mediated T cell exclusion increases tumor surveillance by CD8 T cells and renders tumors more responsive to anti-PD-1 treatment.
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