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Your search keyword '"Coffelt, S. B."' showing total 10 results
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10 results on '"Coffelt, S. B."'

1. Specialized Tfh cell subsets driving type-1 and type-2 humoral responses in lymphoid tissue

Author

Kumar, S, Basto, A, Ribeiro, F, Almeida, S, Campos, P, Peres, C, Pulvirenti, N, Al-Khalidi, S, Kilbey, A, Tosello, J, Piaggio, E, Russo, M, Gama-Carvalho, M, Coffelt, S, Roberts, E, Geginat, J, Florindo, H, Graca, L, Kumar S., Basto A. P., Ribeiro F., Almeida S. C. P., Campos P., Peres C., Pulvirenti N., Al-Khalidi S., Kilbey A., Tosello J., Piaggio E., Russo M., Gama-Carvalho M., Coffelt S. B., Roberts E. W., Geginat J., Florindo H. F., Graca L., Kumar, S, Basto, A, Ribeiro, F, Almeida, S, Campos, P, Peres, C, Pulvirenti, N, Al-Khalidi, S, Kilbey, A, Tosello, J, Piaggio, E, Russo, M, Gama-Carvalho, M, Coffelt, S, Roberts, E, Geginat, J, Florindo, H, Graca, L, Kumar S., Basto A. P., Ribeiro F., Almeida S. C. P., Campos P., Peres C., Pulvirenti N., Al-Khalidi S., Kilbey A., Tosello J., Piaggio E., Russo M., Gama-Carvalho M., Coffelt S. B., Roberts E. W., Geginat J., Florindo H. F., and Graca L.

Abstract

Effective antibody responses are essential to generate protective humoral immunity. Different inflammatory signals polarize T cells towards appropriate effector phenotypes during an infection or immunization. Th1 and Th2 cells have been associated with the polarization of humoral responses. However, T follicular helper cells (Tfh) have a unique ability to access the B cell follicle and support the germinal center (GC) responses by providing B cell help. We investigated the specialization of Tfh cells induced under type-1 and type-2 conditions. We first studied homogenous Tfh cell populations generated by adoptively transferred TCR-transgenic T cells in mice immunized with type-1 and type-2 adjuvants. Using a machine learning approach, we established a gene expression signature that discriminates Tfh cells polarized towards type-1 and type-2 response, defined as Tfh1 and Tfh2 cells. The distinct signatures of Tfh1 and Tfh2 cells were validated against datasets of Tfh cells induced following lymphocytic choriomeningitis virus (LCMV) or helminth infection. We generated single-cell and spatial transcriptomics datasets to dissect the heterogeneity of Tfh cells and their localization under the two immunizing conditions. Besides a distinct specialization of GC Tfh cells under the two immunizations and in different regions of the lymph nodes, we found a population of Gzmk+ Tfh cells specific for type-1 conditions. In human individuals, we could equally identify CMV-specific Tfh cells that expressed Gzmk. Our results show that Tfh cells acquire a specialized function under distinct types of immune responses and with particular properties within the B cell follicle and the GC.

Published
2024

6. Serial measurements of serum human epididymal protein 4 in patients at risk for ovarian cancer.

Author

Stiekema, A., Lok, C. A. R., v Beurden, M., Coffelt, S. B., van Driel, W. J., Kenter, G. G., and Korse, C. M.

Abstract

Objective: Patients with a BRCA1 or BRCA2 gene mutation have an increased lifetime risk of developing epithelial ovarian cancer (EOC). Screening with CA125 and ultrasound is ineffective for detection of EOC at an early stage and does not reduce the mortality rate of EOC. Therefore, women at risk of developing ovarian cancer are recommended to have risk-reducing salpingo-oophorectomy (RRSO). The benefit of the serum marker human epididymis protein 4 (HE4) in screening programmes is still unknown. Therefore, the authors evaluated serial serum HE4 measurements in patients at high risk of developing EOC based on a familiar or genetic predisposition. Materials and Methods: Patients with BRCA1 or BRCA2 mutation or familiar predisposition that developed EOC during screening were selected from the hospital based cancer registry. HE4 was measured in consecutive serum samples. Results: Cross-linking the hospital-based cancer registry with the serum bank resulted in 182 patients who had developed EOC between 1994 and 2013. More than one serum sample was available of 52 patients but of these only seven patients underwent regular screening. HE4 demonstrated a rapid increase in serum levels just before or at time of diagnosis instead of a longer lead time before diagnosis. This is comparable to the concentrations of serum CA125 in consecutive samples. Conclusion: This is the first study showing that serum HE4 values suddenly increase just before diagnosis and do not precede the development of symptoms. This does not support the use of HE4 with a fixed cut-off value for screening in patients at high risk for EOC. [ABSTRACT FROM AUTHOR]

Published
2017
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7. Incidence of lymph node metastases in clinical early-stage mucinous and seromucinous ovarian carcinoma: a retrospective cohort study.

Author

Baal, JOAM, Van de Vijver, KK, Coffelt, SB, Noort, V, Driel, WJ, Kenter, GG, Buist, MR, Lok, CAR, van Baal, Joam, Van de Vijver, K K, Coffelt, S B, van der Noort, V, van Driel, W J, Kenter, G G, and Buist, M R

Subjects
LYMPH node diseases, OVARIAN cancer diagnosis, LYMPH node cancer, METASTASIS, TUMORS, DIAGNOSIS, LONGITUDINAL method, LYMPH nodes, OVARIAN tumors, PROGNOSIS, TUMOR classification, DISEASE incidence, ACQUISITION of data, RETROSPECTIVE studies, TUMOR grading
Abstract

Objective: The use of lymph node sampling during staging procedures in clinical early-stage mucinous ovarian carcinoma (MOC) is an ongoing matter of debate. Furthermore, the incidence of lymph node metastases (LNM) in MOC in relation to tumour grade (G) is unknown. We aimed to determine the incidence of LNM in clinical early-stage MOC per tumour grade.Design: Retrospective study with data from the Dutch Pathology Registry (PALGA).Setting: The Netherlands, 2002-2012.Population or Sample: Patients with MOC.Methods: Histology reports on patients with MOC diagnosed in the Netherlands between 2002 and 2012 were obtained from PALGA. Reports were reviewed for diagnosis, tumour grade and presence of LNM. Clinical data, surgery reports and radiology reports of patients with LNM were retrieved from hospital files.Main Outcome Measures: Incidence of LNM, disease-free survival (DFS).Results: Of 915 patients with MOC, 426 underwent lymph node sampling. Cytoreductive surgery was performed in 267 patients. The other 222 patients received staging without lymph node sampling. In eight of 426 patients, LNM were discovered by sampling. In four of 190 (2.1%) patients with G1 MOC, LNM were present, compared with one of 115 (0.9%) patients with G2 MOC and three of 22 (13.6%) patients with G3 MOC. Tumour grade was not specified in 99 patients. Patients with clinical early-stage MOC had no DFS benefit from lymph node sampling.Conclusions: LNM are rare in early-stage G1 and G2 MOC without clinical suspicion of LNM. Therefore, lymph node sampling can be omitted in these patients.Tweetable Abstract: Lymph node sampling can be omitted in clinical early-stage G1 and G2 mucinous ovarian cancer. [ABSTRACT FROM AUTHOR]

Published
2017
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9. TIE2-expressing macrophages limit the therapeutic efficacy of the vascular-disrupting agent combretastatin A4 phosphate in mice

Author

Abigail F. Welford, Michele De Palma, Seth B. Coffelt, Luigi Naldini, Silvia Nucera, Gillian M. Tozer, Ferdinando Pucci, Matthew Fisher, Claire E. Lewis, Daniela Biziato, Clelia Di Serio, Welford, A. F., Biziato, D., Coffelt, S. B., Nucera, S., Fisher, M., Pucci, F., DI SERIO, Mariaclelia, Naldini, L., De Palma, M., Tozer, G. M., and Lewis, C. E.

Subjects
Receptors, CXCR4, Chemokine, Pathology, medicine.medical_specialty, Transgene, Mammary Neoplasms, Animal, Mice, Transgenic, Cell Separation, CXCR4, Flow cytometry, Mice, Necrosis, 03 medical and health sciences, 0302 clinical medicine, Stilbenes, medicine, Animals, Receptor, 030304 developmental biology, 0303 health sciences, medicine.diagnostic_test, biology, Brief Report, Macrophages, Receptor Protein-Tyrosine Kinases, General Medicine, Hypoxia (medical), Flow Cytometry, Antineoplastic Agents, Phytogenic, Receptor, TIE-2, Angiopoietin receptor, Chemokine CXCL12, 3. Good health, 030220 oncology & carcinogenesis, Cancer research, biology.protein, Female, Tumor necrosis factor alpha, medicine.symptom, Neoplasm Transplantation
Abstract

Vascular-disrupting agents (VDAs) such as combretastatin A4 phosphate (CA4P) selectively disrupt blood vessels in tumors and induce tumor necrosis. However, tumors rapidly repopulate after treatment with such compounds. Here, we show that CA4P-induced vessel narrowing, hypoxia, and hemorrhagic necrosis in murine mammary tumors were accompanied by elevated tumor levels of the chemokine CXCL12 and infiltration by proangiogenic TIE2-expressing macrophages (TEMs). Inhibiting TEM recruitment to CA4P-treated tumors either by interfering pharmacologically with the CXCL12/CXCR4 axis or by genetically depleting TEMs in tumor-bearing mice markedly increased the efficacy of CA4P treatment. These data suggest that TEMs limit VDA-induced tumor injury and represent a potential target for improving the clinical efficacy of VDA-based therapies.

Published
2011
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10. Incidence of lymph node metastases in clinical early-stage mucinous and seromucinous ovarian carcinoma: a retrospective cohort study.

Author

van Baal J, Van de Vijver KK, Coffelt SB, van der Noort V, van Driel WJ, Kenter GG, Buist MR, and Lok C

Subjects
Adenocarcinoma, Mucinous mortality, Adult, Aged, Cohort Studies, Disease-Free Survival, Female, Humans, Incidence, Lymph Nodes pathology, Middle Aged, Neoplasm Grading, Neoplasm Staging, Netherlands epidemiology, Ovarian Neoplasms mortality, Registries, Retrospective Studies, Adenocarcinoma, Mucinous pathology, Lymphatic Metastasis pathology, Ovarian Neoplasms pathology
Abstract

Objective: The use of lymph node sampling during staging procedures in clinical early-stage mucinous ovarian carcinoma (MOC) is an ongoing matter of debate. Furthermore, the incidence of lymph node metastases (LNM) in MOC in relation to tumour grade (G) is unknown. We aimed to determine the incidence of LNM in clinical early-stage MOC per tumour grade., Design: Retrospective study with data from the Dutch Pathology Registry (PALGA)., Setting: The Netherlands, 2002-2012., Population or Sample: Patients with MOC., Methods: Histology reports on patients with MOC diagnosed in the Netherlands between 2002 and 2012 were obtained from PALGA. Reports were reviewed for diagnosis, tumour grade and presence of LNM. Clinical data, surgery reports and radiology reports of patients with LNM were retrieved from hospital files., Main Outcome Measures: Incidence of LNM, disease-free survival (DFS)., Results: Of 915 patients with MOC, 426 underwent lymph node sampling. Cytoreductive surgery was performed in 267 patients. The other 222 patients received staging without lymph node sampling. In eight of 426 patients, LNM were discovered by sampling. In four of 190 (2.1%) patients with G1 MOC, LNM were present, compared with one of 115 (0.9%) patients with G2 MOC and three of 22 (13.6%) patients with G3 MOC. Tumour grade was not specified in 99 patients. Patients with clinical early-stage MOC had no DFS benefit from lymph node sampling., Conclusions: LNM are rare in early-stage G1 and G2 MOC without clinical suspicion of LNM. Therefore, lymph node sampling can be omitted in these patients., Tweetable Abstract: Lymph node sampling can be omitted in clinical early-stage G1 and G2 mucinous ovarian cancer., (© 2016 Royal College of Obstetricians and Gynaecologists.)

Published
2017
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