ArticleClinical & translational immunology2019
Tissue-specific tumor microenvironments influence responses to immunotherapies.
Article in Clinical & translational immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- NPLOC4 Constructs Tumor Immunosuppressive Microenvironment in Pan-cancer and Hepatocellular Carcinoma.Current medicinal chemistry · 2026Article
- YTHDF3 suppresses interferon-stimulated gene (ISG)-dependent antitumor immunity and promotes HPV carcinogenesis in cervical cancer.Cell death & disease · 2025Article
- Neurodegeneration rewires the tumor microenvironment via the neuro-immune-cancer axis.iScience · 2025Review
- Myeloid-Derived LGALS9-P4HB Immune Interaction Promotes Metastasis in Gastric Cancer Through Enhanced Cell Proliferation and Lipid Metabolism.Journal of cellular and molecular medicine · 2025Article
- Immunosuppressive microenvironment of liver restrains chemotherapeutic efficacy in triple-negative breast cancer.Journal for immunotherapy of cancer · 2025Article
- Increases in 4-Acetaminobutyric Acid Generated by Phosphomevalonate Kinase Suppress CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- PIK3CA mutation-driven immune signature as a prognostic marker for evaluating the tumor immune microenvironment and therapeutic response in breast cancer.Journal of cancer research and clinical oncology · 2024Article
- Effectiveness of immune checkpoint inhibitor therapy on bone metastases in non-small-cell lung cancer.Frontiers in immunology · 2024Article
- Development and Validation of a Prognostic Risk Model for Patients with Advanced Melanoma Treated with Immune Checkpoint Inhibitors.The oncologist · 2023Article
- Advances in PD-1 signaling inhibition-based nano-delivery systems for tumor therapy.Journal of nanobiotechnology · 2023Review
- Article
- Editorial: Combining chemo/radio therapy and immunotherapy for cancers-perfect mix of old and new.Frontiers in immunology · 2022Article
- Progesterone promotes immunomodulation and tumor development in the murine mammary gland.Journal for immunotherapy of cancer · 2021Article
- Tissues and Tumor Microenvironment (TME) in 3D: Models to Shed Light on Immunosuppression in Cancer.Cells · 2021Review
- Atezolizumab alleviates the immunosuppression induced by PD‑L1‑positive neutrophils and improves the survival of mice during sepsis.Molecular medicine reports · 2021Article
- Pattern Recognition Receptors (PRRs) in Macrophages Possess Prognosis and Immunotherapy Potential for Melanoma.Frontiers in immunology · 2021Article
- The Crosstalk Between Tumor Cells and the Immune Microenvironment in Breast Cancer: Implications for Immunotherapy.Frontiers in oncology · 2021Review
- Article
- Primary and metastatic breast tumors cross-talk to influence immunotherapy responses.Oncoimmunology · 2020Article
- Cancer patient stratification based on the tumor microenvironment.Journal of thoracic disease · 2020Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesInvestigation of variable response rates to cancer immunotherapies has exposed the immunosuppressive tumor microenvironment (TME) as a limiting factor of therapeutic efficacy. A determinant of TME composition is the tumor location, and clinical data have revealed associations between certain metastatic sites and reduced responses. Preclinical models to study tissue-specific TMEs have eliminated genetic heterogeneity, but have investigated models with limited clinical relevance.
methodsWe investigated the TMEs of tumors at clinically relevant sites of metastasis (liver and lungs) and their impact on αPD-1/αCTLA4 and trimAb (αDR5, α4-1BB, αCD40) therapy responses in the 67NR mouse breast cancer and Renca mouse kidney cancer models.
resultsTumors grown in the lungs were resistant to both therapies whereas the same tumor lines growing in the mammary fat pad (MFP), liver or subcutaneously could be completely eradicated, despite greater tumor burden. Assessment of tumor cells and drug delivery in 67NR lung or MFP tumors revealed no differences and prompted investigation into the immune TME. Lung tumors had a more immunosuppressive TME with increased myeloid-derived suppressor cell infiltration, decreased T cell infiltration and activation, and decreased NK cell activation. Depletion of various immune cell subsets indicated an equivalent role for NK cells and CD8
conclusionTaken together, these data demonstrate that tissue-specific TMEs influence immunotherapy responses and highlight the importance in defining tissue-specific response patterns in patients.
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