Abstract PO-22: Compromised counterselection by FAS creates a lethal subtype of germinal center lymphoma
| العنوان: | Abstract PO-22: Compromised counterselection by FAS creates a lethal subtype of germinal center lymphoma |
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| المؤلفون: | Jagan R. Muppidi, Olga Plotnikova, Moyi Li, Nikita Kotlov, George E. Wright, Raud Razzaghi, Chen Yao, Shreya Agarwal, James D. Phelan, Stefania Pittaluga, Krystle Nomie, David W. Scott, John J. O'Shea, Da-Wei Huang, Katsuyoshi Takata |
| المصدر: | Blood Cancer Discovery. 1:PO-22 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Cell, Germinal center, General Medicine, Biology, medicine.disease, Fas ligand, Lymphoma, medicine.anatomical_structure, Antigen, hemic and lymphatic diseases, medicine, Cancer research, Receptor, Gene, Homeostasis |
| الوصف: | Fas is highly expressed on germinal center (GC) B cells, and mutations of FAS have been reported in diffuse large B-cell lymphoma (DLBCL); however, the function of Fas in the GC remains controversial. Although GC-derived DLBCL has better overall outcomes to therapy than other DLBCL types, some cases are refractory and the molecular basis for this is often unknown. We show that Fas is a strong cell-intrinsic regulator of GC B cells that promotes B-cell death in the light zone likely via T follicular helper (Tfh) cell-derived Fas ligand. In the absence of Fas, GCs were more clonally diverse due to an accumulation of cells that did not demonstrably bind antigen. We found that FAS alterations occurred most commonly in the GC-derived genetic subtype of DLBCL, EZB. FAS alterations in EZB were associated with inferior outcomes and an enrichment of Tfh cells. Alterations in FAS co-occurred with deficiency in HVEM and PD-1 ligands that regulate the Tfh-B cell interaction and were associated with increased diversity of B-cell receptor variable genes across samples. This work shows that Fas is critically required for GC homeostasis and suggests that loss of Tfh-mediated counterselection in the GC contributes to lethality in a distinct subtype of GC-derived lymphoma. Citation Format: Raud Razzaghi, Shreya Agarwal, Nikita Kotlov, Olga Plotnikova, Krystle Nomie, Da Wei Huang, George W. Wright, Moyi Li, Katsuyoshi Takata, Chen Yao, John J. O'Shea, James D. Phelan, Stefania Pittaluga, David W. Scott, Jagan R. Muppidi. Compromised counterselection by FAS creates a lethal subtype of germinal center lymphoma [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-22. |
| تدمد: | 2643-3249 2643-3230 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::32532330594360fd17507ca81223b380Test https://doi.org/10.1158/2643-3249.lymphoma20-po-22Test |
| رقم الانضمام: | edsair.doi...........32532330594360fd17507ca81223b380 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 26433249 26433230 |
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