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1مؤتمر
المؤلفون: Vu, Quyen, Jhaveri, Niyati, Pratapa, Aditya, Paustian, Christopher, Moudgil, Tarsem, Rajamanickam, Venkatesh, Simons, Noah, Braubach, Oliver, Leidner, Rom S, Fox, Bernard A, Jensen, Shawn M
المصدر: Regular and Young Investigator Award Abstracts
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2مؤتمر
المؤلفون: Iwamoto, Noriko, Minegishi, Yuriko, Ueda, Koji, Koguchi, Yoshinobu, Redmond, William L, Piening, Brian, Fox, Bernard A, Tran, Eric, Shimada, Takashi
المصدر: Regular and Young Investigator Award Abstracts
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3مؤتمر
المؤلفون: Paustian, Christopher, Moudgil, Tarsem, Rajamanickam, Venkatesh, Simons, Noah, Meng, Ryan, Couey, Marcus, Taylor, Matthew H, Koguchi, Yoshinobu, Stadum, Annie, Christie, Tanisha, Hulett, Tyler, Iwamoto, Noriko, Shimada, Takashi, Minegishi, Yuriko, Vu, Quyen, Redmond, William L, Rushforth, Lessli, Peterson, Abigail, Bernard, Brady, Bryan Bell, R, Bifulco, Carlo, Ueda, Koji, Hilton, Traci, Jensen, Shawn M, Hu, Hong-Ming, Piening, Brian, Urba, Walter J, Fox, Bernard A, Leidner, Rom S
المصدر: Regular and Young Investigator Award Abstracts
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4مؤتمر
المؤلفون: Meng, Ryan, Moudgil, Tarsem, Iwamoto, Noriko, Minegishi, Yuriko, Koguchi, Yoshinobu, Rajamanickam, Venkatesh, Christie, Tanisha, Redmond, William L, Bifulco, Carlo, Hilton, Traci, Dowdell, Alexa, Jensen, Shawn M, Sanborn, Rachel E, Hu, Hong-Ming, Bryan Bell, R, Urba, Walter J, Leidner, Rom S, Ueda, Koji, Shimada, Takashi, Piening, Brian, Fox, Bernard A
المصدر: Regular and Young Investigator Award Abstracts
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5مؤتمر
المؤلفون: Muijlwijk, Tara, Nijenhuis, Dennis NLM, Ganzevles, Sonja H, Brink, Arjen, Ke, Changlin, Fass, Joseph N, Rajamanickam, Venkatesh, Rene Leemans, C, Koguchi, Yoshinobu, Fox, Bernard A, Poell, Jos B, Brakenhoff, Ruud H, Ven, Rieneke van de
المصدر: Regular and Young Investigator Award Abstracts
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6مؤتمر
المؤلفون: Minegishi, Yuriko, Iwamoto, Noriko, Shimada, Takashi, Kiyotani, Kazuma, Nagayama, Satoshi, Tran, Eric, Koguchi, Yoshinobu, Redmond, William L, Piening, Brian, Fox, Bernard A, Ueda, Koji
المصدر: Regular and Young Investigator Award Abstracts
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7دورية أكاديمية
المؤلفون: Qualliotine, Jesse R, Nakagawa, Takuya, Rosenthal, Sara Brin, Sadat, Sayed, Ballesteros-Merino, Carmen, Xu, Guorong, Mark, Adam, Nasamran, Art, Gutkind, J Silvio, Fisch, Kathleen M, Guo, Theresa, Fox, Bernard A, Khan, Zubair, Molinolo, Alfredo A, Califano, Joseph A
المصدر: Cancers, vol 15, iss 17
مصطلحات موضوعية: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Genetics, 2.1 Biological and endogenous factors, Aetiology, network analysis, head and neck squamous cell carcinoma, human papillomavirus, HPV, oropharyngeal neoplasms, epigenetics, exome sequencing, The Cancer Genome Atlas
الوقت: 4379
الوصف: HPV-associated oropharynx carcinoma (HPVOPC) tumors have a relatively low mutational burden. Elucidating the relative contributions of other tumor alterations, such as DNA methylation alterations, alternative splicing events (ASE), and copy number variation (CNV), could provide a deeper understanding of carcinogenesis drivers in this disease. We applied network propagation analysis to multiple classes of tumor alterations in a discovery cohort of 46 primary HPVOPC tumors and 25 cancer-unaffected controls and validated our findings with TCGA data. We identified significant overlap between differential gene expression networks and all alteration classes, and this association was highest for methylation and lowest for CNV. Significant overlap was seen for gene clusters of G protein-coupled receptor (GPCR) pathways. HPV16-human protein interaction analysis identified an enriched cluster defined by an immune-mediated GPCR signal, including CXCR3 cytokines CXCL9, CXCL10, and CXCL11. CXCR3 was found to be expressed in primary HPVOPC, and scRNA-seq analysis demonstrated CXCR3 ligands to be highly expressed in M2 macrophages. In vivo models demonstrated decreased tumor growth with antagonism of the CXCR3 receptor in immunodeficient but not immunocompetent mice, suggesting that the CXCR3 axis can drive tumor proliferation in an autocrine fashion, but the effect is tempered by an intact immune system. In conclusion, methylation, ASE, and SNV alterations are highly associated with network gene expression changes in HPVOPC, suggesting that ASE and methylation alterations have an important role in driving the oncogenic phenotype. Network analysis identifies GPCR networks, specifically the CXCR3 chemokine axis, as modulators of tumor-immune interactions that may have proliferative effects on primary tumors as well as a role for immunosurveillance; however, CXCR3 inhibition should be used with caution, as these agents may both inhibit and stimulate tumor growth considering the competing effects of this cytokine axis. Further ...
وصف الملف: application/pdf
العلاقة: qt9x30p0hz; https://escholarship.org/uc/item/9x30p0hzTest
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8دورية أكاديمية
المؤلفون: Di Giacomo, Anna Maria, Lahn, Michael, Eggermont, Alexander Mm, Fox, Bernard, Ibrahim, Ramy, Sharma, Padmanee, Allison, James P, Maio, Michele
المصدر: Articles, Abstracts, and Reports
مصطلحات موضوعية: Humans, CTLA-4 Antigen, T-Lymphocytes, Cytotoxic, Neoplasms, Italy, Immunotherapy, oregon, chiles, Oncology
الوصف: The 2022 yearly Think Tank Meeting in Siena, Tuscany (Italy), organized by the Italian Network for Tumor Biotherapy (NIBIT) Foundation, the Parker Institute for Cancer Immunotherapy and the World Immunotherapy Council, included a focus on the future of integrating and expanding the use of targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). The conference members exchanged their views on the lessons from targeting CTLA-4 and compared the effect to the impact of blocking Programmed cell death protein 1 (PD1) or its ligand (PDL1). The increasing experience with both therapeutic approaches and their combination suggests that targeting CTLA-4 may lead to more durable responses for a sizeable proportion of patients, though the specific mechanism is not entirely understood. Overcoming toxicity of blocking CTLA-4 is currently being addressed with different doses and dose regimens, especially when combined with PD1/PDL1 blocking antibodies. Novel therapeutics targeting CTLA-4 hold the promise to reduce toxicities and thus allow different combination strategies in the future. On the whole, the consent was that targeting CTLA-4 remains an important strategy to improve the efficacy of cancer immunotherapies.
العلاقة: https://digitalcommons.providence.org/publications/8488Test; https://pubmed.ncbi.nlm.nih.gov/38169219Test/
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9دورية أكاديمية
المؤلفون: Muijlwijk, Tara, Nijenhuis, Dennis N L M, Ganzevles, Sonja H, Brink, Arjen, Ke, Changlin, Fass, Joseph, Rajamanickam, Venkatesh, Leemans, C René, Koguchi, Yoshinobu, Fox, Bernard A, Poell, Jos B, Brakenhoff, Ruud H, van de Ven, Rieneke
المصدر: Articles, Abstracts, and Reports
مصطلحات موضوعية: Humans, Squamous Cell Carcinoma of Head and Neck, Programmed Cell Death 1 Receptor, Head and Neck Neoplasms, Carcinoma, Squamous Cell, RNA, Tumor Microenvironment, Lymphocytes, Tumor-Infiltrating, T-Lymphocytes, chiles, oregon, Neurosciences, Oncology, Otolaryngology
الوصف: BACKGROUND: The response rate to immune checkpoint inhibitors targeting programmed cell death 1 (PD-1) receptor is 13%-18% for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Detailed understanding of the tumor immune microenvironment (TIME) is crucial in order to explain and improve this response rate. HNSCCs arise at various anatomical locations including the oral cavity, hypopharynx, larynx and oropharynx. Studies directly comparing immune infiltration between anatomical sites are scarce. Since the distinct locations could drive deviating microenvironments, we questioned whether the immune composition varies across these HNSCC sites. METHODS: Here, we characterized the TIME of 76 fresh tumor specimens using flow cytometry and performed single-cell RNA-sequencing on nine head and neck tumor samples. RESULTS: We found major differences in the composition of the TIME between patients. When comparing anatomical sites: tumors originating from the oral cavity had higher T cell infiltrates than tumors from other anatomical sites. The percentage of tumor-infiltrating T-lymphocytes positive for the immune checkpoint PD-1 varied considerably between patients, with the highest fraction of PD-1+ T cells found in larynx squamous cell carcinomas (SCCs). While we had hypothesized that the anatomical sites of tumor origin would drive sample clustering, our data showed that the type of TIME was more dominant and was particularly driven by the fraction of T cells positive for PD-1. Moreover, a high proportion of PD-1+ CD8+ T cells associated with an improved overall survival. Using single-cell RNA-sequencing, we observed that PD-1 expression was highest in the CD8-ENTPD1 tissue resident memory T cell/exhausted T cell and CD4-CXCL13 type 1 T helper cell clusters. CONCLUSIONS: We found that oral cavity SCCs had the highest frequencies of T cells. We also observed considerable interpatient heterogeneity for PD-1 on T cells, with noticeably higher frequencies of PD-1+ CD4+ T helper cells in ...
العلاقة: https://digitalcommons.providence.org/publications/8472Test; https://www.ncbi.nlm.nih.gov/pubmed/38212122Test
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10دورية أكاديمية
المؤلفون: Fox, Bernard
المصدر: Articles, Abstracts, and Reports
مصطلحات موضوعية: oregon, chiles, Immunotherapy, Oncology
الوصف: NCI Distinguished Lecturer Series
