B-Lymphocytes in the Pathophysiology of Pancreatic Adenocarcinoma

Minici, Claudia; Testoni, Sabrina Gloria Giulia; Della‐Torre, Emanuel

doi:10.3389/fimmu.2022.867902

Cited by 16 publications

(19 citation statements)

References 148 publications

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“…Under hypoxic conditions, CXCL13 secreted by CAFs attracts immunosuppressive B cells to tumors [ 88 ], which can then induce M2 polarization of TAMs [ 89 ]. In addition, B cells can activate CAFs via the soluble factor platelet derived growth factor-B (PDGF-B) [ 90 , 91 ]. It is difficult to reconcile the pro-tumor role of B cells in mice with developing tumors with the human data from well-established tumors.…”

Section: Pdac Is Defined By An Immunosuppressive Tmementioning

confidence: 99%

Clinical Strategies Targeting the Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma

Skorupan

Domínguez

Ricci

et al. 2022

Cancers

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Pancreatic cancer has a complex tumor microenvironment which engages in extensive crosstalk between cancer cells, cancer-associated fibroblasts, and immune cells. Many of these interactions contribute to tumor resistance to anti-cancer therapies. Here, new therapeutic strategies designed to modulate the cancer-associated fibroblast and immune compartments of pancreatic ductal adenocarcinomas are described and clinical trials of novel therapeutics are discussed. Continued advances in our understanding of the pancreatic cancer tumor microenvironment are generating stromal and immune-modulating therapeutics that may improve patient responses to anti-tumor treatment.

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Section: Pdac Is Defined By An Immunosuppressive Tmementioning

confidence: 99%

Clinical Strategies Targeting the Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma

Skorupan

Domínguez

Ricci

et al. 2022

Cancers

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“…The cancer could promote the production of these circulating factors. The lymphocytes widely involved in the pathophysiology of minimal change disease [ 29 ] and in the modulation of immune response in sepsis [ 30 ] and cancer [ 31 ] could be a keystone in the mechanism of our findings.…”

Section: Discussionmentioning

confidence: 83%

Association between proteinuria trajectories and outcomes in critically ill patients with sepsis or shock

et al. 2022

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Background Proteinuria results from kidney damage and can be a predictor of illness severity and mortality in the intensive care unit (ICU). However, the optimal timing of proteinuria measurements and the reference values remain undetermined. Our objective was to identify the patterns of proteinuria change associated with mortality in ICU patients with sepsis or shock. Methods This monocentric retrospective cohort study performed from April 2010 to April 2018 involved all ICU patients with sepsis or shock and at least two measurements of proteinuria from a 24h-urine collection during the first 10 days of ICU stay, the first of which was made within 48h after ICU admission. We identified proteinuria trajectories by a semi-parametric mixture model and analysed the association between the trajectories and the mortality at day 28 by Cox proportional-hazards model. Results A total of 3,344 measurements of proteinuria from 659 patients were analysed. Four proteinuria trajectories were identified. Trajectories 1, 2, 3 and 4 comprised 127, 421, 60 and 51 patients, and were characterized by a first proteinuria of 1.14 [0.66–1.55], 0.52 [0.26–0.91], 2.92 [2.38–3.84] and 2.58 [1.75–3.32] g/24h (p<0.001) and a mortality of 24.4%, 38%, 20% and 43% (p = 0.002), respectively. Trajectories 3 and 4 had a high first proteinuria (>2g/24h). Only, the proteinuria of trajectory 4 increased within 3 days following the first measurement and was associated with increased mortality at day 28 (hazard ratio: 2.36 95%CI [1.07–5.19], p = 0.03), regardless of acute renal failure. The factors associated with trajectory 4 were cancer (relative risk: 8.91 95%CI [2.09–38.02], p = 0.003) and use of inotropic drugs (relative risk: 0.17 95%CI [0.04–0.69], p = 0.01). Conclusion This exploratory study of ICU patients with sepsis or shock identified four proteinuria trajectories with distinct patterns of proteinuria change over time and mortality rates. These results provide novel insights into renal pathophysiology and may be helpful to investigate subphenotypes of kidney injury among ICU patients in future studies.

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“…B lymphocytes display dual roles in the tumor microenvironment, which can be either anti-tumorigenic or pro-tumorigenic ( 21 ). Tumor-infiltrating B cells maturate and differentiate into IgG1-producing plasma cells and memory B cells in ectopic lymph nodes like tertiary lymphoid structures (TLS) with the help of follicular helper Tfh cells ( 2 , 20 , 22 ) ( Figure 1 ). Memory and plasma B cells in TME respond to tumor-associated antigens by producing IgG1 and IgE antibodies that activate the complement system, phagocytosis, or antibody-dependent cytotoxicity of NK cells and macrophages ( 23 – 25 ).…”

Section: Roles Of B Cells In Pdacmentioning

confidence: 99%

“…Furthermore, greater Breg levels in the peripheral blood of PDAC patients correlated with worse overall survival. To investigate the involvement of B cells in PDAC progression, pancreatic cancer cell lines, human peripheral blood & pancreatic tissue samples, xenografts, or genetically-engineered murine models (KPC, KC, and orthotopic) have been utilized ( 13 , 20 , 46 , 47 ).…”

Section: Roles Of B Cells In Pdacmentioning

confidence: 99%

“…The PDAC-TME is inhabited by B-cell subsets with either pro-tumorigenic or antitumorigenic properties. Anti-tumorigenic B cells have a strong tumor suppressive activity by presenting tumor antigens to T cells and producing anti-tumor antibodies (IgG1), but specific protumorigenic B lymphocyte subsets, namely, regulatory B (Breg) cells secrete immunosuppressive cytokines such as IL-10 and IL-35 thereby p romoting cancer p ro gr es si o n an d e va d i n g immunosurveillance in PDAC (20).…”

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confidence: 99%

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Pancreatic cancer: Emerging field of regulatory B-cell-targeted immunotherapies

et al. 2023

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Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer, is characterized by a high mortality rate and poor prognosis. Current treatments for PDAC, are ineffective due to a prominent immunosuppressive PDAC tumor microenvironment (TME). Although B lymphocytes are highly infiltrated into PDAC, the importance of B lymphocytes in tumorigenesis is largely neglected. B cells play a dual role in the PDAC tumor microenvironment, acting as either anti-tumorigenic or pro-tumorigenic depending on where they are localized. Tumor-infiltrating B cells, which reside in ectopic lymph nodes, namely tertiary lymphoid structures (TLS), produce anti-tumor antibodies and present tumor antigens to T cells to contribute to cancer immunosurveillance. Alternatively, regulatory B cells (Bregs), dispersed inside the TME, contribute to the dampening of anti-tumor immune responses by secreting anti-inflammatory cytokines (IL-10 and IL-35), which promote tumor growth and metastasis. Determining the role of Bregs in the PDAC microenvironment is thus becoming increasingly attractive for developing novel immunotherapeutic approaches. In this minireview, we shed light on the emerging role of B cells in PDAC development and progression, with an emphasis on regulatory B cells (Bregs). Furthermore, we discussed the potential link of Bregs to immunotherapies in PDAC. These current findings will help us in understanding the full potential of B cells in immunotherapy.

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B-Lymphocytes in the Pathophysiology of Pancreatic Adenocarcinoma

Cited by 16 publications

References 148 publications

Clinical Strategies Targeting the Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma

Clinical Strategies Targeting the Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma

Association between proteinuria trajectories and outcomes in critically ill patients with sepsis or shock

Pancreatic cancer: Emerging field of regulatory B-cell-targeted immunotherapies

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