ArticleFrontiers in immunology2015
NKG2D is a Key Receptor for Recognition of Bladder Cancer Cells by IL-2-Activated NK Cells and BCG Promotes NK Cell Activation.
Article in Frontiers in immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 44 citations in OpenAlex.
- Ethnicity-specific molecular subtypes and a machine-learning risk model in Asian patients with non-muscle-invasive bladder cancer.Scientific reports · 2026Article
- Epigenetic modulation elicits an NK cell-mediated immune response in urothelial carcinoma.Molecular medicine (Cambridge, Mass.) · 2025Article
- BCG therapy in bladder cancer and its tumor microenvironment interactions.Clinical microbiology reviews · 2025Review
- Differential Role of NKG2A/HLA-E Interaction in the Outcomes of Bladder Cancer Patients Treated withBiomedicines · 2025Article
- BCG priming followed by a novel interleukin combination activates Natural Killer cells to selectively proliferate and become anti-tumour long-lived effectors.Scientific reports · 2024Article
- Advances in tumor microenvironment and underlying molecular mechanisms of bladder cancer: a systematic review.Discover oncology · 2024Review
- Innate Lymphoid Cells in Bladder Cancer: From Mechanisms of Action to Immune Therapies.Cancer immunology research · 2024Review
- High and selective cytotoxicity of ex vivo expanded allogeneic human natural killer cells from peripheral blood against bladder cancer: implications for natural killer cell instillation after transurethral resection of bladder tumor.Journal of experimental & clinical cancer research : CR · 2024Article
- Immunomodulatory effects of exercise in cancer prevention and adjuvant therapy: a narrative review.Frontiers in physiology · 2023Review
- Intravesical BCG in patients with non-muscle invasive bladder cancer induces trained immunity and decreases respiratory infections.Journal for immunotherapy of cancer · 2023Observational
- The present and future of immunocytokines for cancer treatment.Cellular and molecular life sciences : CMLS · 2022Review
- CyTOF analysis identifies unusual immune cells in urine of BCG-treated bladder cancer patients.Frontiers in immunology · 2022Article
- Gender Differences in Urothelial Bladder Cancer: Effects of Natural Killer Lymphocyte Immunity.Journal of clinical medicine · 2021Review
- Endoplasmic Reticulum Stress and Tumor Microenvironment in Bladder Cancer: The Missing Link.Frontiers in cell and developmental biology · 2021Review
- Natural Killer Anti-Tumor Activity Can Be Achieved byFrontiers in immunology · 2021Article
- A Transcriptional Signature of IL-2 Expanded Natural Killer Cells Predicts More Favorable Prognosis in Bladder Cancer.Frontiers in immunology · 2021Article
- ZNF652-Induced circRHOT1 Promotes SMAD5 Expression to Modulate Tumorigenic Properties and Nature Killer Cell-Mediated Toxicity in Bladder Cancer via Targeting miR-3666.Journal of immunology research · 2021Article
- Harnessing Natural Killer Cell Function for Genitourinary Cancers.The Urologic clinics of North America · 2020Review
- Impact of exercise on the immune system and outcomes in hematologic malignancies.Blood advances · 2020Review
- Identification of gene expression profiles and immune cell infiltration signatures between low and high tumor mutation burden groups in bladder cancer.International journal of medical sciences · 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
Intravesical instillation of bacillus Calmette-Guérin (BCG) is used to treat superficial bladder cancer, either papillary tumors (after transurethral resection) or high-grade flat carcinomas (carcinoma in situ), reducing recurrence in about 70% of patients. Initially, BCG was proposed to work through an inflammatory response, mediated by phagocytic uptake of mycobacterial antigens and cytokine release. More recently, other immune effectors such as monocytes, natural killer (NK), and NKT cells have been suggested to play a role in this immune response. Here, we provide a comprehensive study of multiple bladder cancer cell lines as putative targets for immune cells and evaluated their recognition by NK cells in the presence and absence of BCG. We describe that different bladder cancer cells can express multiple activating and inhibitory ligands for NK cells. Recognition of bladder cancer cells depended mainly on NKG2D, with a contribution from NKp46. Surprisingly, exposure to BCG did not affect the immune phenotype of bladder cells nor increased NK cell recognition of purified IL-2-activated cell lines. However, NK cells were activated efficiently when BCG was included in mixed lymphocyte cultures, suggesting that NK activation after mycobacteria treatment requires the collaboration of various immune cells. We also analyzed the percentage of NK cells in peripheral blood of a cohort of bladder cancer patients treated with BCG. The total numbers of NK cells did not vary during treatment, indicating that a more detailed study of NK cell activation in the tumor site will be required to evaluate the response in each patient.
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