scholarly journals Upregulation of CD20 Positive B-Cells and B-Cell Aggregates in the Tumor Infiltration Zone is Associated with Better Survival of Patients with Pancreatic Ductal Adenocarcinoma

2020 ◽  
Vol 21 (5) ◽  
pp. 1779 ◽  
Author(s):  
Maximilian Brunner ◽  
Katharina Maier ◽  
Petra Rümmele ◽  
Anne Jacobsen ◽  
Susanne Merkel ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cells ◽  
B Cell ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Ductal Adenocarcinoma ◽  
Cell Aggregates ◽  
Tumor Infiltration ◽  
Long Term Survivors

Patients with pancreatic ductal adenocarcinoma (PDAC) normally have a poor long-term prognosis. However, some rare cases of long-term survivors have been reported. The tumor microenvironment, consisting of cellular and stromal components, possibly plays an important role and might influence prognosis. In this context, the role of tumor-infiltrating B-cells and its impact on the survival in patients with PDAC remains controversial. We therefore aimed to assess the prognostic value of CD20-positive B-cells and CD20-positive B-cell aggregates as well as CD138, IgM, Pax5, and Ki67 on the survival of patients with PDAC using immunohistochemistry of FFPE pancreatectomy tissue sections from patients that underwent primary surgery for pT3- and R0-pancreatic adenocarcinoma between 1995 and 2016. Patients with PDAC were matched and grouped in 16 long-term-survivors (LTS, median overall survival (OS): 96 months [range: 61–177 months]) and 16 short-term-survivors (STS, median OS: 16 months [range: 7–32 months]). CD20-positive B-cells and B-cell aggregates in the tumor infiltration zone were significantly upregulated in the LTS-group compared to the STS-group (p = 0.0499 respectively p = 0.0432). Regarding the entire patient cohort (n = 32) CD20 positive B-cell aggregates in the tumor infiltration zone were an independent prognostic marker for overall survival in multivariate analysis (HR 9.2, CI 1.6–51.4, p = 0.012). These results underline the importance of tumor-associated B-cells for prognosis of patients with PDAC. The detailed role of B cells in the pathomechanism of PDAC should be further investigated for predicting outcome, identifying appropriate treatment regimens, and developing novel therapeutic options.

scholarly journals A Retrospective Analysis of Long-Term Survivors with Metastatic Pancreatic Ductal Adenocarcinoma

2013 ◽  
Vol 24 ◽  
pp. ix47
Author(s):  
H. Hayashi ◽  
S. Kondo ◽  
S. Shiba ◽  
Y. Sakamoto ◽  
C. Morizane ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Retrospective Analysis ◽  
Ductal Adenocarcinoma ◽  
Long Term Survivors

Mutation profiles in long-term survivors with pulmonary metastases from pancreatic ductal adenocarcinoma

Pancreatology ◽  
2017 ◽  
Vol 17 (3) ◽  
pp. S83
Author(s):  
Masato Ono ◽  
Toru Namamura ◽  
Toshiaki Shichinohe ◽  
Keisuke Okamura ◽  
Takhiro Tsuchikawa ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Pulmonary Metastases ◽  
Ductal Adenocarcinoma ◽  
Long Term Survivors

scholarly journals Long‐Term Survivors in Metastatic Pancreatic Ductal Adenocarcinoma: A Retrospective and Matched Pair Analysis

2019 ◽  
Vol 24 (12) ◽  
pp. 1543-1548 ◽  
Author(s):  
Pauline Rochefort ◽  
Audrey Lardy‐Cleaud ◽  
Matthieu Sarabi ◽  
Françoise Desseigne ◽  
Anne Cattey‐Javouhey ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Ductal Adenocarcinoma ◽  
Matched Pair ◽  
Matched Pair Analysis ◽  
Long Term Survivors ◽  
Pair Analysis

scholarly journals B Cell-Specific Expression of Ataxia-Telangiectasia Mutated Protein Kinase Promotes Chronic Gammaherpesvirus Infection

2017 ◽  
Vol 91 (19) ◽  
Author(s):  
Eric J. Darrah ◽  
Joseph M. Kulinski ◽  
Wadzanai P. Mboko ◽  
Gang Xin ◽  
Laurent P. Malherbe ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Ataxia Telangiectasia ◽  
Chronic Infection ◽  
Viral Latency ◽  
Viral Reactivation ◽  
Ataxia Telangiectasia Mutated

ABSTRACT Manipulation of host cellular pathways is a strategy employed by gammaherpesviruses, including mouse gammaherpesvirus 68 (MHV68), in order to negotiate a chronic infection. Ataxia-telangiectasia mutated (ATM) plays a unique yet incompletely understood role in gammaherpesvirus infection, as it has both proviral and antiviral effects. Chronic gammaherpesvirus infection is poorly controlled in a host with global ATM insufficiency, whether the host is a mouse or a human. In contrast, ATM facilitates replication, reactivation, and latency establishment of several gammaherpesviruses in vitro, suggesting that ATM is proviral in the context of infected cell cultures. The proviral role of ATM is also evident in vivo, as myeloid-specific ATM expression facilitates MHV68 reactivation during the establishment of viral latency. In order to better understand the complex relationship between host ATM and gammaherpesvirus infection, we depleted ATM specifically in B cells, a cell type critical for chronic gammaherpesvirus infection. B cell-specific ATM deficiency attenuated the establishment of viral latency due to compromised differentiation of ATM-deficient B cells. Further, we found that during long-term infection, peritoneal B-1b, but not related B-1a, B cells display the highest frequency of gammaherpesvirus infection. While ATM expression did not affect gammaherpesvirus tropism for B-1 B cells, B cell-specific ATM expression was necessary to support viral reactivation from peritoneal cells during long-term infection. Thus, our study reveals a role of ATM as a host factor that promotes chronic gammaherpesvirus infection of B cells. IMPORTANCE Gammaherpesviruses infect a majority of the human population and are associated with cancer, including B cell lymphomas. ATM is a unique host kinase that has both proviral and antiviral roles in the context of gammaherpesvirus infection. Further, there is insufficient understanding of the interplay of these roles in vivo during chronic infection. In this study, we show that ATM expression by splenic B cells is required for efficient establishment of gammaherpesvirus latency. We also show that ATM expression by peritoneal B cells is required to facilitate viral reactivation during long-term infection. Thus, our study defines a proviral role of B cell-specific ATM expression during chronic gammaherpesvirus infection.

Long-term survivors after pancreatic ductal adenocarcinoma resection: An actual 5-year analysis of overall and post-recurrence survival

Pancreatology ◽  
2021 ◽  
Vol 21 ◽  
pp. S84
Author(s):  
G. Belfiori ◽  
S. Crippa ◽  
F. Aleotti ◽  
G. Gasparini ◽  
D. Tamburrino ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Ductal Adenocarcinoma ◽  
Long Term Survivors

scholarly journals Alterations in B Cell and Follicular T-Helper Cell Subsets in Patients with Acute COVID-19 and COVID-19 Convalescents

2021 ◽  
Vol 44 (1) ◽  
pp. 194-205
Author(s):  
Igor V. Kudryavtsev ◽  
Natalia A. Arsentieva ◽  
Oleg K. Batsunov ◽  
Zoia R. Korobova ◽  
Irina V. Khamitova ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Humoral Immunity ◽  
N Protein ◽  
Follicular Helper ◽  
Healthy Donors ◽  
Specific Igg ◽  
Sparse Methods

Background. Humoral immunity requires interaction between B cell and T follicular helper cells (Tfh) to produce effective immune response, but the data regarding a role of B cells and Tfh in SARS-CoV-2 defense are still sparse. Methods. Blood samples from patients with acute COVID-19 (n = 64), convalescents patients who had specific IgG to SARS-CoV-2 N-protein (n = 55), and healthy donors with no detectable antibodies to any SARS-CoV-2 proteins (HC, n = 44) were analyses by multicolor flow cytometry. Results. Patients with acute COVID-19 showed decreased levels of memory B cells subsets and increased proportion plasma cell precursors compared to HC and COVID-19 convalescent patients, whereas for the latter the elevated numbers of virgin naïve, Bm2′ and “Bm3+Bm4” was found if compared with HC. During acute COVID-19 CXCR3+CCR6− Tfh1-like cells were decreased and the levels of CXCR3–CCR6+ Tfh17-like were increased then in HC and convalescent patients. Finally, COVID-19 convalescent patients had increased levels of Tfh2-, Tfh17- and DP Tfh-like cells while comparing their amount with HC. Conclusions. Our data indicate that COVID-19 can impact the humoral immunity in the long-term.

B-cell treatment in ANCA-associated vasculitis

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_3) ◽  
pp. iii68-iii73
Author(s):  
Alexandre Karras ◽  
Hélène Lazareth ◽  
Sophie Chauvet
Keyword(s):  
B Cells ◽  
B Cell ◽  
Optimal Dose ◽  
B Cell Depletion ◽  
Anca Vasculitis ◽  
Anca Associated Vasculitis ◽  
Cell Subpopulations ◽  
Anti Cd20

Abstract The pivotal role of B-cells in ANCA-associated vasculitis has been suggested by experimental data that demonstrate the direct pathogenicity of ANCAs. Rituximab (RTX), an anti-CD20 monoclonal antibody that targets B-cells, has proven its efficacy for induction of remission in severe ANCA vasculitis. RTX is equivalent to CYC for induction of remission, and is probably superior in relapsing patients. Long-term B cell depletion by prolonged RTX treatment has been shown to significantly reduce the relapse rate, when compared with AZA maintenance therapy. Biomarkers, such as B-cell subpopulations or ANCA monitoring, may help the clinician to determine the optimal dose and duration of RTX therapy.

Interleukin-1β-induced pancreatitis promotes pancreatic ductal adenocarcinoma via B lymphocyte–mediated immune suppression

Gut ◽  
2020 ◽  
pp. gutjnl-2019-319912 ◽  
Author(s):  
Ryota Takahashi ◽  
Marina Macchini ◽  
Masaki Sunagawa ◽  
Zhengyu Jiang ◽  
Takayuki Tanaka ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
B Cells ◽  
B Cell ◽  
Pancreatic Ductal Adenocarcinoma ◽  
B Lymphocytes ◽  
B Lymphocyte ◽  
Cell Activity ◽  
Interleukin 1Β ◽  
Cell Infiltration ◽  
Ductal Adenocarcinoma

ObjectiveLong-standing chronic pancreatitis is an established risk factor for pancreatic ductal adenocarcinoma (PDAC). Interleukin-1β (IL-1β) has been associated in PDAC with shorter survival. We employed murine models to investigate the mechanisms by which IL-1β and chronic pancreatitis might contribute to PDAC progression.DesignWe crossed LSL-Kras+/G12D;Pdx1-Cre (KC) mice with transgenic mice overexpressing IL-1β to generate KC-IL1β mice, and followed them longitudinally. We used pancreatic 3D in vitro culture to assess acinar-to-ductal metaplasia formation. Immune cells were analysed by flow cytometry and immunohistochemical staining. B lymphocytes were adoptively transferred or depleted in Kras-mutant mice. B-cell infiltration was analysed in human PDAC samples.ResultsKC-IL1β mice developed PDAC with liver metastases. IL-1β treatment increased Kras+/G12D pancreatic spheroid formation. CXCL13 expression and B lymphocyte infiltration were increased in KC-IL1β pancreata. Adoptive transfer of B lymphocytes from KC-IL1β mice promoted tumour formation, while depletion of B cells prevented tumour progression in KC-IL1β mice. B cells isolated from KC-IL1β mice had much higher expression of PD-L1, more regulatory B cells, impaired CD8+ T cell activity and promoted tumorigenesis. IL-35 was increased in the KC-IL1β pancreata, and depletion of IL-35 decreased the number of PD-L1+ B cells. Finally, in human PDAC samples, patients with PDAC with higher B-cell infiltration within tumours showed significantly shorter survival.ConclusionWe show here that IL-1β promotes tumorigenesis in part by inducing an expansion of immune-suppressive B cells. These findings point to the growing significance of B suppressor cells in pancreatic tumorigenesis.

Sign in / Sign up

Export Citation Format

Share Document