ArticleOncotarget2015
Distribution and prognostic relevance of tumor-infiltrating lymphocytes (TILs) and PD-1/PD-L1 immune checkpoints in human brain metastases.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.
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Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 123 citations in OpenAlex.
- Prognostic Value of Programmed Death Ligand-1 Expression in Solid Tumors Irrespective of Immunotherapy Exposure: A Systematic Review and Meta-Analysis.Molecular diagnosis & therapy · 2022Pooled it
- Spatially-resolved single-cell imaging of melanoma brain metastases identifies localized immune patterns predictive of immune checkpoint blockade response.Neuro-oncology · 2026Article
- Future directions in the treatment of brain metastases: evaluating the role of cellular players in the tumour microenvironment.Acta neuropathologica · 2026Review
- Effect of combining targeted therapies or chemotherapy with stereotactic radiosurgery (SRS) on the prognosis of patients with brain metastases from non-small cell lung cancer (NSCLC).Journal of neuro-oncology · 2025Article
- Biomarkers of immunotherapy response in neuro-oncology.Neuro-oncology advances · 2025Review
- Research progress of anti-angiogenic therapy combined with immunotherapy and radiotherapy for the treatment of brain metastases in non-small cell lung cancer (Review).Oncology letters · 2025Review
- Altered CD4 T cell response in oligometatastic non-small cell lung cancer brain metastasis.Acta neuropathologica communications · 2025Article
- Integrated analysis of molecular and clinical features associated with overall survival in melanoma patients with brain metastasis.Acta neuropathologica communications · 2025Article
- Molecular Underpinnings of Brain Metastases.International journal of molecular sciences · 2025Review
- Progress in personalized immunotherapy for patients with brain metastasis.NPJ precision oncology · 2025Review
- Spatial Multiomics Reveals Intratumoral Immune Heterogeneity with Distinct Cytokine Networks in Lung Cancer Brain Metastases.Cancer research communications · 2024Article
- IMMUNE AND MOLECULAR CORRELATES OF RESPONSE TO IMMUNOTHERAPY REVEALED BY BRAIN-METASTATIC MELANOMA MODELS.bioRxiv : the preprint server for biology · 2024Article
- Tumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment.Nature communications · 2023Article
- Single-cell transcriptomic analyses provide insights into the cellular origins and drivers of brain metastasis from lung adenocarcinoma.Neuro-oncology · 2023Article
- Impact of prior systemic therapy on lymphocytic infiltration in surgically resected breast cancer brain metastases.Breast cancer research and treatment · 2023Article
- The immune cell landscape of glioblastoma patients highlights a myeloid-enriched and immune suppressed microenvironment compared to metastatic brain tumors.Frontiers in immunology · 2023Article
- Immune related biomarkers for cancer metastasis to the brain.Experimental hematology & oncology · 2022Review
- A comprehensive profiling of the immune microenvironment of breast cancer brain metastases.Neuro-oncology · 2022Article
- Molecular matched targeted therapies for primary brain tumors-a single center retrospective analysis.Journal of neuro-oncology · 2022Article
- Where Are We Now and Where Might We Be Headed in Understanding and Managing Brain Metastases in Colorectal Cancer Patients?Current treatment options in oncology · 2022Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 12 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The activation of immune cells by targeting checkpoint inhibitors showed promising results with increased patient survival in distinct primary cancers. Since only limited data exist for human brain metastases, we aimed at characterizing tumor infiltrating lymphocytes (TILs) and expression of immune checkpoints in the respective tumors. Two brain metastases cohorts, a mixed entity cohort (n = 252) and a breast carcinoma validation cohort (n = 96) were analyzed for CD3+, CD8+, FOXP3+, PD-1+ lymphocytes and PD-L1+ tumor cells by immunohistochemistry. Analyses for association with clinico-epidemiological and neuroradiological parameters such as patient survival or tumor size were performed. TILs infiltrated brain metastases in three different patterns (stromal, peritumoral, diffuse). While carcinomas often show a strong stromal infiltration, TILs in melanomas often diffusely infiltrate the tumors. Highest levels of CD3+ and CD8+ lymphocytes were seen in renal cell carcinomas (RCC) and strongest PD-1 levels on RCCs and melanomas. High amounts of TILs, high ratios of PD-1+/CD8+ cells and high levels of PD-L1 were negatively correlated with brain metastases size, indicating that in smaller brain metastases CD8+ immune response might get blocked. PD-L1 expression strongly correlated with TILs and FOXP3 expression. No significant association of patient survival with TILs was observed, while high levels of PD-L1 showed a strong trend towards better survival in melanoma brain metastases (Log-Rank p = 0.0537). In summary, melanomas and RCCs seem to be the most immunogenic entities. Differences in immunotherapeutic response between tumor entities regarding brain metastases might be attributable to this finding and need further investigation in larger patient cohorts.
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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.