Spatial distribution of B cells predicts prognosis in human pancreatic adenocarcinoma

Giovanni Francesco Castino, Nina Cortese, Giovanni Capretti, Simone Serio, Giuseppe Di Caro, R. Mineri, Elena Magrini, Fabio Grizzi, Paola Cappello, Franco Novelli, Paola Spaggiari, Massimo Roncalli, Cristina Ridolfi, Francesca Gavazzi, Alessandro Zerbi, Paola Allavena, Federica Marchesi

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Abstract

ABSTRACT: 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.

Original languageEnglish
JournalOncoImmunology
Volume5
Issue number4
DOIs
Publication statusPublished - Apr 2 2016

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Keywords

  • B cells
  • biomarkers
  • immunotherapy
  • pancreatic adenocarcinoma (PDAC)
  • tertiary lymphoid tissue

ASJC Scopus subject areas

  • Immunology and Allergy
  • Oncology
  • Immunology

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