Anti-CD5 monoclonal antibody, clone DWT6 [FITC]

The immune microenvironment of pancreatic ductal adenocarcinoma (PDA) is comprised of a heterogeneous population of cells that are critical for disease evolution. Prominent among these are the specialized CD1d(hi)CD5(+) regulatory B (B-reg) cells that exert a pro-tumorigenic role by promoting tumor cell proliferation. Dissecting the molecular pathways regulating this immune sub-population can thus be valuable for uncovering potential therapeutic targets. Here, we investigate Bruton's tyrosine kinase (BTK), a key B-cell kinase, as a potential regulator of CD1d(hi)CD5(+) B-reg differentiation in the pancreatic tumor microenvironment. Treatment of cytokine-induced B cells in vitro with the high specificity BTK inhibitor Tirabrutinib inhibited CD1d(hi)CD5(+) B-reg differentiation and production of IL-10 and IL-35, essential mediators of B-reg immunosuppressive functions. The BTK signaling pathway was also found to be active in vivo in PanIN-associated regulatory B cells. Tirabrutinib treatment of mice bearing orthotopic Kras(G12D)-pancreatic lesions severely compromised stromal accumulation of the CD1d(hi)CD5(+) B-reg population. This was accompanied by an increase in stromal CD8(+)IFN gamma(+) cytotoxic T cells and significant attenuation of tumor cell proliferation and PanIN growth. Our results uncover a novel role for BTK in regulating CD1d(hi)CD5(+) B-reg differentiation and emphasize its potential as a therapeutic target for pancreatic cancer.

Herein we report the case of a 41-year-old woman who presented with pelvic pain. Magnetic Resonance Imaging exhibited a single pelvic mass, measuring 50 mm long axis, alongside the right iliac vessels. Histological examination of the excision specimen showed a lymphoid tumor with features of localized Castleman disease, hyaline vascular type. Moreover we identified multiple interfollicular dark clusters, composed of cells morphologically resembling cortical thymocytes. Their immunophenotype was consistent with an intermediate stage of T-cell differentiation, with the expression of CD3, CD4, CD8, TdT, CD1a, CD99, CD2, CD5, CD7 and CD10, with 40% Ki67. After integration of clinical and molecular data, the retained diagnosis was an indolent T-cell lymphoblastic proliferation associated with hyaline vascular localized Castleman disease. The clinical course confirmed the indolent nature of the proliferation, despite a late local recurrence at 7 years of the initial diagnosis, without histological modification, due to an incomplete initial resection surgery. (C) 2018 Elsevier Masson SAS. All rights reserved.