Intratumoral CD4+ T cells mediate anti-tumor cytotoxicity in human bladder cancer
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PROVIDER: PRJNA629542 | ENA |
REPOSITORIES: ENA
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Project description:Responses to anti-PD-1 immunotherapy occur but are infrequent in bladder cancer. The specific T cells that mediate tumor rejection are unknown. T cells from human bladder tumors and non-malignant tissue were assessed with single-cell RNA and paired T cell receptor (TCR) sequencing of 30,604 T cells from 7 patients. We find that the states and repertoire of CD8+ T cells are not altered in tumors compared with non-malignant tissues. In contrast, single-cell analysis of CD4+ T cells demonstrates several tumor-specific states, including multiple distinct states of regulatory T cells. Surprisingly, we also find multiple cytotoxic CD4+ T cell states that are clonally expanded. These CD4+ T cells can kill autologous tumor in an MHC class II-dependent fashion and are suppressed by regulatory T cells. Further, a gene signature of cytotoxic CD4+ T cells in tumors predicts a clinical response in 244 metastatic bladder cancer patients treated with anti-PD-L1.
2020-06-01 | GSE149652 | GEO
Project description:Responses to anti-PD-1 immunotherapy occur but are infrequent in bladder cancer. The specific T cells that mediate tumor rejection are unknown. T cells from human bladder tumors and non-malignant tissue were assessed with single-cell RNA and paired T cell receptor (TCR) sequencing of 30,604 T cells from 7 patients. We find that the states and repertoires of CD8+ T cells are not distinct in tumors compared with non-malignant tissues. In contrast, single-cell analysis of CD4+ T cells demonstrates several tumor-specific states, including multiple distinct states of regulatory T cells. Surprisingly, we also find multiple cytotoxic CD4+ T cell states that are clonally expanded. These CD4+ T cells can kill autologous tumors in an MHC class II-dependent fashion and are suppressed by regulatory T cells. Further, a gene signature of cytotoxic CD4+ T cells in tumors predicts a clinical response in 244 metastatic bladder cancer patients treated with anti-PD-L1.
| S-EPMC7321885 | biostudies-literature
Project description:Background: Frankincense (Ru Xiang) and sandalwood (Tan Xiang) are ingredients used in traditional Chinese medicine, and have been recognized as cancer preventive and therapeutic agents. Hydrodistillation of frankincense gum resins and sandalwood heartwood to prepare essential oils is a method to extract biologically active ingredients from these plant-derived products. This study was designed to differentiate frankincense (Boswellia carterii) and sandalwood (Santalum album) induced anti-proliferative and pro-apoptotic activities in cultured human bladder cancer cells. Methods: Frankincense and sandalwood essential oils-mediated cytotoxicity was studied in established human bladder cancer J82 cells and immortalized normal human bladder urothelial UROtsa cells using a colorimetric assay. Essential oils-activated gene expression and pathway activation in human bladder cancer J82 cells were identified using high density microarray and bioinformatics techniques. Results: Human bladder cancer cells were more sensitive to immortalized normal bladder cells with suppressed viability following frankincense essential oil exposure. In contrast, both cancerous and normal bladder cells responded to sandalwood essential with similar levels of cytotoxicity. Based on microarray and bioinformatics analyses, genes responsible for suppressing biological processes and apoptosis were induced in J82 cells by both essential oils. Although both frankincense and sandalwood essential oils activated common ontologies and canonical pathways leading to suppressed J82 cell viability and apoptosis, each essential oil had unique property on these cells. For example, heat shock proteins and histone core were ongologies regulated by frankincense essential oil, whereas transcription regulation and G-protein couple receptor were ontologies unique to sandalwood essential oil treatment. In addition, NRF-2 mediated oxidative stress was implicated as the primary cause of frankincense essential oil-induced J82 cell death; in contrast, DNA damage and cell cycle arrest might be attributed to sandalwood essential oil-mediated cytotoxicity. Conclusion: Based on cell biology and comprehensive gene expression analysis, our results provide a preliminary, yet focused characterization of genetic responses to frankincense and sandalwood essential oils with respect to their proposed anti-neoplastic properties. Modern biomedical technologies are powerful tools to study biological responses following treatments with traditional Chinese medicine, which always consist of complex chemical constituents. To differentiate mechanisms of frankincense and sandalwood essential oils induced cytotoxicty in bladder cancer J82 cells, time-dependent transcriptoms expression was performed in cultured cells following essential oils treatments
2014-06-10 | E-GEOD-53171 | biostudies-arrayexpress
Project description:Malignant Schwann cell precursors mediate intratumoral plasticity in human neuroblastoma
| PRJNA616343 | ENA
Project description:Malignant Schwann cell precursors mediate intratumoral plasticity in human neuroblastoma [Array]
| PRJNA616347 | ENA
Project description:Epigenetic priming to enhance CAR-T cell cytotoxicity in bladder cancer
| PRJNA692221 | ENA
Project description:Background: Frankincense (Ru Xiang) and sandalwood (Tan Xiang) are ingredients used in traditional Chinese medicine, and have been recognized as cancer preventive and therapeutic agents. Hydrodistillation of frankincense gum resins and sandalwood heartwood to prepare essential oils is a method to extract biologically active ingredients from these plant-derived products. This study was designed to differentiate frankincense (Boswellia carterii) and sandalwood (Santalum album) induced anti-proliferative and pro-apoptotic activities in cultured human bladder cancer cells. Methods: Frankincense and sandalwood essential oils-mediated cytotoxicity was studied in established human bladder cancer J82 cells and immortalized normal human bladder urothelial UROtsa cells using a colorimetric assay. Essential oils-activated gene expression and pathway activation in human bladder cancer J82 cells were identified using high density microarray and bioinformatics techniques. Results: Human bladder cancer cells were more sensitive to immortalized normal bladder cells with suppressed viability following frankincense essential oil exposure. In contrast, both cancerous and normal bladder cells responded to sandalwood essential with similar levels of cytotoxicity. Based on microarray and bioinformatics analyses, genes responsible for suppressing biological processes and apoptosis were induced in J82 cells by both essential oils. Although both frankincense and sandalwood essential oils activated common ontologies and canonical pathways leading to suppressed J82 cell viability and apoptosis, each essential oil had unique property on these cells. For example, heat shock proteins and histone core were ongologies regulated by frankincense essential oil, whereas transcription regulation and G-protein couple receptor were ontologies unique to sandalwood essential oil treatment. In addition, NRF-2 mediated oxidative stress was implicated as the primary cause of frankincense essential oil-induced J82 cell death; in contrast, DNA damage and cell cycle arrest might be attributed to sandalwood essential oil-mediated cytotoxicity. Conclusion: Based on cell biology and comprehensive gene expression analysis, our results provide a preliminary, yet focused characterization of genetic responses to frankincense and sandalwood essential oils with respect to their proposed anti-neoplastic properties. Modern biomedical technologies are powerful tools to study biological responses following treatments with traditional Chinese medicine, which always consist of complex chemical constituents.
2014-06-10 | GSE53171 | GEO
Project description:Frankincense oil is prepared from aromatic hardened wood resin obtained by tapping Boswellia trees. For thousands of years, it has been important both socially and economically as an ingredient in incense and perfumes. Frankincense oil is a botanical oil distillate made from fermented plants that contains boswellic acid, a component known to have anti-neoplastic properties. We evaluated frankincense oil-induced cytotoxicity in bladder cancer cells. With a window of concentration, frankincense oil suppressed cell viability and induced cytotoxicity in bladder transitional carcinoma J82 cells but not normal bladder urothelial UROtsa cells immortalized with SV40 large T antigen. However, frankincense oil-induced J82 cell death did not result in DNA fragmentation. Microarray and bioinformatics analysis confirmed that frankincense oil activated cell cycle arrest, suppressed cell proliferation, and activated apoptosis in J82 cells through a series of potential pathways. These finding suggest that bladder cancer can be treated through intravesical administration of pharmaceutical agents similar to direct application on melanoma. 2E05 J82 cells were untreated or treated with a 1/1000 dilution of frankincense oil for 0.5, 1, 2, or 3 hours prior to RNA extraction.
2009-02-09 | E-GEOD-14002 | biostudies-arrayexpress
Project description:Intravesical BCG Immunotherapy is the standard of care in treating non-muscle invasive bladder cancer, yet its mechanism of action remains elusive. Both innate and adaptive immune responses have been implicated in BCG activity. While prior research has indirectly demonstrated the importance of T cells and shown a rise in CD4+ T cells in bladder tissue after BCG, T cell subpopulations have not been fully characterized. We investigated the relationship between effector and regulatory T cells in an immune competent, clinically relevant rodent model of bladder cancer. Our data demonstrate that cancer progression in the MNU rat model of bladder cancer is characterized by a decline in the CD8/FoxP3 ratio, consistent with decreased adaptive immunity. By contrast, treatment with intravesical BCG leads to a large, transient rise in the CD4+ T cell population in the urothelium, and is both more effective and immunogenic compared to intravesical chemotherapy. Interestingly, whole transcriptome expression profiling of post-treatment intravesical CD4+ and CD8+ T cells revealed minimal differences in gene expression after BCG treatment. Together, our results suggest that while BCG induces T cell recruitment to the bladder, the T cell phenotype does not markedly change, implying that combining T cell activating agents with BCG might improve clinical activity.
2017-08-31 | GSE93940 | GEO
Project description:Frankincense oil is prepared from aromatic hardened wood resin obtained by tapping Boswellia trees. For thousands of years, it has been important both socially and economically as an ingredient in incense and perfumes. Frankincense oil is a botanical oil distillate made from fermented plants that contains boswellic acid, a component known to have anti-neoplastic properties. We evaluated frankincense oil-induced cytotoxicity in bladder cancer cells. With a window of concentration, frankincense oil suppressed cell viability and induced cytotoxicity in bladder transitional carcinoma J82 cells but not normal bladder urothelial UROtsa cells immortalized with SV40 large T antigen. However, frankincense oil-induced J82 cell death did not result in DNA fragmentation. Microarray and bioinformatics analysis confirmed that frankincense oil activated cell cycle arrest, suppressed cell proliferation, and activated apoptosis in J82 cells through a series of potential pathways. These finding suggest that bladder cancer can be treated through intravesical administration of pharmaceutical agents similar to direct application on melanoma.
2009-02-10 | GSE14002 | GEO