+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Spatial distribution of B cells predicts prognosis in human pancreatic adenocarcinoma



Spatial distribution of B cells predicts prognosis in human pancreatic adenocarcinoma



Oncoimmunology 5(4): E1085147



B-cell responses are emerging as critical regulators of cancer progression. In this study, we investigated the role of B lymphocytes in the microenvironment of human pancreatic ductal adenocarcinoma (PDAC), in a retrospective consecutive series of 104 PDAC patients and in PDAC preclinical models. Immunohistochemical analysis revealed that B cells occupy two histologically distinct compartments in human PDAC, either scatteringly infiltrating (CD20-TILs), or organized in tertiary lymphoid tissue (CD20-TLT). Only when retained within TLT, high density of B cells predicted longer survival (median survival 16.9 mo CD20-TLThi vs. 10.7 mo CD20-TLTlo; p = 0.0085). Presence of B cells within TLT associated to a germinal center (GC) immune signature, correlated with CD8-TIL infiltration, and empowered their favorable prognostic value. Immunotherapeutic vaccination of spontaneously developing PDAC (KrasG12D-Pdx1-Cre) mice with α-enolase (ENO1) induced formation of TLT with active GCs and correlated with increased recruitment of T lymphocytes, suggesting induction of TLT as a strategy to favor mobilization of immune cells in PDAC. In contrast, in an implanted tumor model devoid of TLT, depletion of B cells with an anti-CD20 antibody reinstated an antitumor immune response. Our results highlight B cells as an essential element of the microenvironment of PDAC and identify their spatial organization as a key regulator of their antitumor function. A mindfully evaluation of B cells in human PDAC could represent a powerful prognostic tool to identify patients with distinct clinical behaviors and responses to immunotherapeutic strategies.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 058882727

Download citation: RISBibTeXText

PMID: 27141376

DOI: 10.1080/2162402x.2015.1085147


Related references

Decreased circadian component Bmal1 predicts tumor progression and poor prognosis in human pancreatic ductal adenocarcinoma. Biochemical and Biophysical Research Communications 472(1): 156-162, 2016

Downregulation of miR-124 predicts poor prognosis in pancreatic ductal adenocarcinoma patients. British Journal of Biomedical Science 73(4): 152-157, 2016

Nanog Predicts Poor Prognosis in Human Pancreatic Cancer and Is Downregulated by QingyihuaJi Formula in Pancreatic Cancer Stem Cells. Evidence-BasedComplementaryandAlternativeMedicine2016:7028289, 2016

Preoperative FDG-PET predicts early recurrence and a poor prognosis after resection of pancreatic adenocarcinoma. Annals of Surgical Oncology 22(2): 677-684, 2015

Low expression of TBX4 predicts poor prognosis in patients with stage II pancreatic ductal adenocarcinoma. International Journal of Molecular Sciences 12(8): 4953-4963, 2011

Elevated expression of CTHRC1 predicts unfavorable prognosis in patients with pancreatic ductal adenocarcinoma. American Journal of Cancer Research 6(8): 1820-1827, 2016

High expression of interleukin-22 and its receptor predicts poor prognosis in pancreatic ductal adenocarcinoma. Annals of Surgical Oncology 21(1): 125-132, 2014

Coexpression of EGFR and CXCR4 predicts poor prognosis in resected pancreatic ductal adenocarcinoma. Plos one 10(2): E0116803, 2015

Increased Tim-3 expression in peripheral NK cells predicts a poorer prognosis and Tim-3 blockade improves NK cell-mediated cytotoxicity in human lung adenocarcinoma. International Immunopharmacology 29(2): 635-641, 2015

Low expression of nucleus accumbens-associated protein 1 predicts poor prognosis for patients with pancreatic ductal adenocarcinoma. Pathology International 62(12): 802-810, 2012

Simultaneous high expression of PLD1 and Sp1 predicts a poor prognosis for pancreatic ductal adenocarcinoma patients. Oncotarget 7(48): 78557-78565, 2016

Loss of p27Kip1 expression independently predicts poor prognosis for patients with resectable pancreatic adenocarcinoma. Cancer 85(6): 1250-1260, 1999

High expression of CX3CL1/CX3CR1 axis predicts a poor prognosis of pancreatic ductal adenocarcinoma. Journal of Gastrointestinal Surgery 16(8): 1493-1498, 2012

Expression of kallikrein-related peptidase 7 predicts poor prognosis in patients with unresectable pancreatic ductal adenocarcinoma. Cancer Epidemiology Biomarkers and Prevention 21(7): 1135-1142, 2012