Local and systemic XAGE-1b-specific immunity in patients with lung adenocarcinoma

• Published in: Cancer Immunology, Immunotherapy Immunotherapy, 2015-09, Vol.64 (9), p.1109-1121
• Main Authors: Talebian Yazdi, Mehrdad, Loof, Nikki M., Franken, Kees L. M. C., Taube, Christian, Oostendorp, Jaap, Hiemstra, Pieter S., Welters, Marij J. P., van der Burg, Sjoerd H.
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - immunology; Adenocarcinoma of Lung; Aged; Aged, 80 and over; Amino Acid Sequence; Antibodies; Antibody Specificity; Antigens; Antigens, Neoplasm - biosynthesis; Antigens, Neoplasm - immunology; Cancer Research; Chemotherapy; Cohort Studies; Enzymes; Female; Humans; Immunology; Immunotherapy; Kinases; Lung cancer; Lung Neoplasms - immunology; Lymphatic system; Lymphocytes; Lymphocytes, Tumor-Infiltrating - immunology; Male; Medicine; Medicine & Public Health; Middle Aged; Molecular Sequence Data; Oncology; Original; Original Article; Proteins; Radiation therapy; T cell receptors; T-Lymphocytes - immunology; White people
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-015-1716-2

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.