ArticlePloS one2018
Urothelial bladder cancer may suppress perforin expression in CD8+ T cells by an ICAM-1/TGFβ2 mediated pathway.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- AllergoOncology in Review: Harnessing Allergy in the Field of Oncology to Improve Patient Outcomes.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2026Review
- T Cell Exhaustion in Hepatocellular Carcinoma: A Substantial Barrier in Immunotherapy.Journal of cellular and molecular medicine · 2026Review
- Extracellular granzyme K enhances PD-L1 transcription and stability via F2RL1 activation to facilitate tumor immune evasion in lung adenocarcinoma.Journal for immunotherapy of cancer · 2026Article
- Cytotoxic T Cells: Kill, Memorize, and Mask to Maintain Immune Homeostasis.International journal of molecular sciences · 2025Review
- Unleashing the therapeutic potential of tumor-draining lymph nodes: spotlight on bladder cancer.Journal of translational medicine · 2025Review
- Nanomaterial-Enhanced Immunotherapy: Advancing T-Cell-Based Treatments for Bladder Cancer.International journal of nanomedicine · 2025Review
- Perforin 1 in Cancer: Mechanisms, Therapy, and Outlook.Biomolecules · 2024Review
- The role of transforming growth factor-β (TGF-β) in the formation of exhausted CD8 + T cells.Clinical and experimental medicine · 2024Review
- CD8 T-cell subsets: heterogeneity, functions, and therapeutic potential.Experimental & molecular medicine · 2023Review
- Inhibition of protein kinase C isozymes causes immune profile alteration and possibly decreased tumorigenesis in bladder cancer.American journal of cancer research · 2023Article
- Epigenetic Modification of PD-1/PD-L1-Mediated Cancer Immunotherapy against Melanoma.International journal of molecular sciences · 2022Review
- Article
- Review
- A novel immune-related gene pair prognostic signature for predicting overall survival in bladder cancer.BMC cancer · 2021Article
- Fewer tumour draining sentinel nodes in patients with progressing muscle invasive bladder cancer, after neoadjuvant chemotherapy and radical cystectomy.World journal of urology · 2020Article
- Identifying Common Genes Related to Platelet and Immunity for Lung Adenocarcinoma Prognosis Prediction.Frontiers in molecular biosciences · 2020Article
- ATM Mutations Benefit Bladder Cancer Patients Treated With Immune Checkpoint Inhibitors by Acting on the Tumor Immune Microenvironment.Frontiers in genetics · 2020Article
- Immune Responses in Bladder Cancer-Role of Immune Cell Populations, Prognostic Factors and Therapeutic Implications.Frontiers in oncology · 2019Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The immune system plays a significant role in urothelial bladder cancer (UBC) progression, with CD8+ T cells being capable to directly kill tumor cells using perforin and granzymes. However, tumors avoid immune recognition by escape mechanisms. In this study, we aim to demonstrate tumor immune escape mechanisms that suppress CD8+ T cells cytotoxicity. 42 patients diagnosed with UBC were recruited. CD8+ T cells from peripheral blood (PB), sentinel nodes (SN), and tumor were analyzed in steady state and in vitro-stimulated conditions by flow cytometry, RT-qPCR, and ELISA. Mass spectrometry (MS) was used for identification of proteins from UBC cell line culture supernatants. Perforin was surprisingly found to be low in CD8+ T cells from SN, marked by 1.8-fold decrease of PRF1 expression, with maintained expression of granzyme B. The majority of perforin-deficient CD8+ T cells are effector memory T (TEM) cells with exhausted Tc2 cell phenotype, judged by the presence of PD-1 and GATA-3. Consequently, perforin-deficient CD8+ T cells from SN are low in T-bet expression. Supernatant from muscle invasive UBC induces perforin deficiency, a mechanism identified by MS where ICAM-1 and TGFβ2 signaling were causatively validated to decrease perforin expression in vitro. Thus, we demonstrate a novel tumor escape suppressing perforin expression in CD8+ T cells mediated by ICAM-1 and TGFβ2, which can be targeted in combination for cancer immunotherapy.
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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.