Local and systemic XAGE-1b-specific immunity in patients with lung adenocarcinomaReportar como inadecuado




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Cancer Immunology, Immunotherapy

, Volume 64, Issue 9, pp 1109–1121

First Online: 30 May 2015Received: 08 December 2014Accepted: 09 May 2015DOI: 10.1007-s00262-015-1716-2

Cite this article as: Talebian Yazdi, M., Loof, N.M., Franken, K.L.M.C. et al. Cancer Immunol Immunother 2015 64: 1109. doi:10.1007-s00262-015-1716-2

Abstract

XAGE-1b is a cancer-testis antigen aberrantly expressed in pulmonary adenocarcinoma. Systemic antibody and T cell responses have been demonstrated in adenocarcinoma patients, but so far, local antigen-specific immunity has not been reported. In this study, XAGE-1b expression by tumor cells as well as the presence of systemic and-or local XAGE-1b-specific immunity was assessed in peripheral blood, tumor tissue and tumor-draining lymph nodes of Caucasian patients with pulmonary adenocarcinoma. XAGE-1b protein expression was detected in 43.6 % 17 of 39 of patients when at least two different parts of a resected tumor were assessed. In 20 patients, analysis of T cells isolated and expanded from the primary tumor and its draining lymph node demonstrated XAGE-1b-specific responses in two patients. XAGE-1b-specific immunoglobulin G antibodies were found in 3 of 40 patients. These three antibody-positive patients had also mounted a systemic T cell response to XAGE-1b, measured by proliferation, cytokine production and expression of T cell activation markers on peripheral blood mononuclear cells. The population of XAGE-1b-specific T cells comprised both CD4+ and CD8+ T cells secreting both type I and II cytokines. Epitope mapping showed that T cells predominantly targeted the N-terminal part of the XAGE-1b protein, while the B cell response was directed against the C-terminal domain. Our study for the first time provides evidence for the presence of XAGE-1b-specific T cells within adenocarcinoma tissue, which supports the concept that XAGE-1b acts as a genuine tumor antigen and, therefore, might form an attractive target for a vaccine-based approach of immunotherapy.

KeywordsXAGE-1b CT antigen Adenocarcinoma Lung cancer AbbreviationsAPCAntigen-presenting cell

B-LCLEBV transformed B cell lines

CBACytometric bead array

CTComputed tomography

ELISAEnzyme-linked immunosorbent assay

ELISPOTEnzyme-linked immunosorbent spot

FCSFetal calf serum

Foxp3Forkhead box P3

IHCImmunohistochemistry

LICRLudwig Institute for Cancer Research

LNLymph node

LUMCLeiden University Medical Center

NSCLCNon-small cell lung cancer

PBMCsPeripheral blood mononuclear cells

PHAPhytohaemagglutinin

RTRoom temperature

TCGFT cell growth factor

TCRT cell receptor

TKITyrosine kinase inhibitors

TILsTumor-infiltrating lymphocytes

Electronic supplementary materialThe online version of this article doi:10.1007-s00262-015-1716-2 contains supplementary material, which is available to authorized users.

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Autor: Mehrdad Talebian Yazdi - Nikki M. Loof - Kees L. M. C. Franken - Christian Taube - Jaap Oostendorp - Pieter S. Hiemstra

Fuente: https://link.springer.com/



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