A set of genes associated with the interferon-γ response of lung cancer patients undergoing α-galactosylceramide-pulsed dendritic cell therapy

Kohsuke Okita, Shinichiro Motohashi, Ryo Shinnakasu, Kaoru Nagato, Kazuki Yamasaki, Yasunori Sato, Hiroshi Kitamura, Atsushi Hijikata, Masakatsu Yamashita, Kanako Shimizu, Shin Ichiro Fujii, Osamu Ohara, Masaru Taniguchi, Isao Sakaida, Toshinori Nakayama

Research output: Contribution to journalArticle

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Abstract

Invariant natural killer T (iNKT) cells possess potent antitumor effects after activation with a specific glycolipid antigen, α-galactosylceramide (αGalCer). A phase I-II clinical study of αGalCer-pulsed dendritic cells (DC) to activate endogenous iNKT cells was previously performed in patients with non-small-cell lung cancer (NSCLC). In this clinical trial, the patients with increased interferon-γ (IFN-γ) production (>two-fold) in PBMC after the DC treatment (good responder group) experienced a prolonged overall survival time in comparison with the poor responder group. We extended the previous study and performed a microarray-based gene expression analysis using peripheral blood CD56 + cells and CD56 - CD3 + T cells from patients enrolled in the above-mentioned clinical study. We sought to identify any biomarkers associated with the immune responses in this immunotherapy trial. Six patient samples corresponding to three subjects in the good responder group and three subjects in the poor responder group were included in the microarray analysis. Genes differentially expressed between pre-treatment and post-treatment samples were selected for analysis. Subsequently, genes that were only expressed in the good responder group or poor responder group were chosen. After these procedures, four selected genes were quantified by reverse transcriptase-polymerase chain reaction in another eight patient samples, and two genes, LTB4DH and DPYSL3, were confirmed to be candidate genes for the predictor of a good immune response. The expression profile of these two genes may be associated with the responsiveness of IFN-γ production after αGalCer-pulsed DC treatment. (Cancer Sci 2010; 101: 2333-2340)

Original languageEnglish
Pages (from-to)2333-2340
Number of pages8
JournalCancer Science
Volume101
Issue number11
DOIs
Publication statusPublished - 2010 Nov 1
Externally publishedYes

Fingerprint

Galactosylceramides
Cell- and Tissue-Based Therapy
Dendritic Cells
Interferons
Lung Neoplasms
Natural Killer T-Cells
Genes
Glycolipids
Therapeutics
Microarray Analysis
Reverse Transcriptase Polymerase Chain Reaction
Transcriptome
Non-Small Cell Lung Carcinoma
Immunotherapy
Blood Cells
Biomarkers
Clinical Trials
T-Lymphocytes
Gene Expression
Antigens

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A set of genes associated with the interferon-γ response of lung cancer patients undergoing α-galactosylceramide-pulsed dendritic cell therapy. / Okita, Kohsuke; Motohashi, Shinichiro; Shinnakasu, Ryo; Nagato, Kaoru; Yamasaki, Kazuki; Sato, Yasunori; Kitamura, Hiroshi; Hijikata, Atsushi; Yamashita, Masakatsu; Shimizu, Kanako; Fujii, Shin Ichiro; Ohara, Osamu; Taniguchi, Masaru; Sakaida, Isao; Nakayama, Toshinori.

In: Cancer Science, Vol. 101, No. 11, 01.11.2010, p. 2333-2340.

Research output: Contribution to journalArticle

Okita, K, Motohashi, S, Shinnakasu, R, Nagato, K, Yamasaki, K, Sato, Y, Kitamura, H, Hijikata, A, Yamashita, M, Shimizu, K, Fujii, SI, Ohara, O, Taniguchi, M, Sakaida, I & Nakayama, T 2010, 'A set of genes associated with the interferon-γ response of lung cancer patients undergoing α-galactosylceramide-pulsed dendritic cell therapy', Cancer Science, vol. 101, no. 11, pp. 2333-2340. https://doi.org/10.1111/j.1349-7006.2010.01696.x
Okita, Kohsuke ; Motohashi, Shinichiro ; Shinnakasu, Ryo ; Nagato, Kaoru ; Yamasaki, Kazuki ; Sato, Yasunori ; Kitamura, Hiroshi ; Hijikata, Atsushi ; Yamashita, Masakatsu ; Shimizu, Kanako ; Fujii, Shin Ichiro ; Ohara, Osamu ; Taniguchi, Masaru ; Sakaida, Isao ; Nakayama, Toshinori. / A set of genes associated with the interferon-γ response of lung cancer patients undergoing α-galactosylceramide-pulsed dendritic cell therapy. In: Cancer Science. 2010 ; Vol. 101, No. 11. pp. 2333-2340.
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AU - Nagato, Kaoru

AU - Yamasaki, Kazuki

AU - Sato, Yasunori

AU - Kitamura, Hiroshi

AU - Hijikata, Atsushi

AU - Yamashita, Masakatsu

AU - Shimizu, Kanako

AU - Fujii, Shin Ichiro

AU - Ohara, Osamu

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AU - Sakaida, Isao

AU - Nakayama, Toshinori

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