ArticleFrontiers in immunology2018
Renal Cell Carcinoma (RCC) Tumors Display Large Expansion of Double Positive (DP) CD4+CD8+ T Cells With Expression of Exhaustion Markers.
Article in Frontiers in immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- Double Positive CD4Frontiers in immunology · 2019Trial
- Unconventional T cells in urological cancers: catch them if you can.Nature reviews. Urology · 2026Review
- Dual stimulation of CD40 and 41BB pathways during ex-vivo TIL expansion enhances CD8+ T cell expansion.bioRxiv : the preprint server for biology · 2026Article
- Case of complete response to immunotherapy in MMR-deficient prostate cancer associated with NK-like and CD4Cell reports. Medicine · 2026Article
- Multi-omics insights for deciphering prognosis-related T cell subsets in hepatocellular carcinoma.Clinical and translational medicine · 2026Article
- MRI of combination immunotherapy in an epithelial ovarian cancer preclinical model.Npj imaging · 2026Article
- The double-positive cells in the tumor microenvironment.Journal of translational internal medicine · 2026Article
- Functionally heterogeneous intratumoral CD4Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- Multicenter validation of CEACAM6 and FOXP3 as robust prognostic biomarkers in colon cancer: Combined immunohistochemical and transcriptomic analysis.Molecular and clinical oncology · 2025Article
- Quantitative analysis of lymphocyte exhaustion markers in patients with localized clear cell renal cell carcinoma.Oncology letters · 2025Article
- Spatial biomarkers of response to eribulin plus pembrolizumab in patients with metastatic triple negative breast cancer in the ENHANCE-1 trial.NPJ breast cancer · 2025Article
- Comprehensive assessment of the association between tumor-infiltrating immune cells and the prognosis of renal cell carcinoma.World journal of clinical oncology · 2024Article
- Spatial iTME analysis of KRAS mutant NSCLC and immunotherapy outcome.NPJ precision oncology · 2024Article
- Kidney double positive T cells have distinct characteristics in normal and diseased kidneys.Scientific reports · 2024Article
- Single-cell profiling of the microenvironment in human bone metastatic renal cell carcinoma.Communications biology · 2024Article
- Upregulated PPP1R14B is connected to cancer progression and immune infiltration in kidney renal clear cell carcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- The basement membrane-related gene signature is associated with immunity and predicts survival accurately in hepatocellular carcinoma.Journal of cancer research and clinical oncology · 2023Article
- Double Positive CD4Cells · 2023Article
- Inflammatory CD4/CD8 double-positive human T cells arise from reactive CD8 T cells and are sufficient to mediate GVHD pathology.Science advances · 2023Article
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11 authors.
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Abstract
Checkpoint inhibitors target the inhibitory receptors expressed by tumor-infiltrating T cells in order to reinvigorate an anti-tumor immune response. Therefore, understanding T cell composition and phenotype in human tumors is crucial. We analyzed by flow cytometry tumor-infiltrating lymphocytes (TILs) from two independent cohorts of patients with different cancer types, including RCC, lung, and colon cancer. In healthy donors, peripheral T cells are usually either CD4+ or CD8+ with a small percentage of CD4+ CD8+ DP cells (<5%). Compared to several other cancer types, including lung, and colorectal cancers, TILs from about a third of RCC patients showed an increased proportion of DP CD4+CD8+ T cells (>5%, reaching 30-50% of T cells in some patients). These DP T cells have an effector memory phenotype and express CD38, 4-1BB, and HLA-DR, suggesting antigen-driven expansion. In fact, TCR sequencing analysis revealed a high degree of clonality in DP T cells. Additionally, there were high levels of PD-1 and TIM-3 expression on DP T cells, which correlated with higher expression of PD-1 and TIM-3 in conventional single positive CD8 T cells from the same patients. These results suggest that DP T cells could be dysfunctional tumor-specific T cells with the potential to be reactivated by checkpoint inhibitors.
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