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Japanese Journal of Clinical Oncology Advance Access published online on October 1, 2009
Japanese Journal of Clinical Oncology, doi:10.1093/jjco/hyp112
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© The Author (2009). Published by Oxford University Press. All rights reserved

Regular Dose of Gemcitabine Induces an Increase in CD14+ Monocytes and CD11c+ Dendritic Cells in Patients with Advanced Pancreatic Cancer

Atsuko Soeda1,2, Yuriko Morita-Hoshi1, Hiroaki Makiyama1, Chigusa Morizane3, Hideki Ueno3, Masafumi Ikeda3, Takuji Okusaka3, Shizuka Yamagata1, Noriko Takahashi1, Ichinosuke Hyodo2, Yoichi Takaue1 and Yuji Heike1

1 Department of Medical Oncology, National Cancer Center Hospital, Tokyo
2 Department of Gastroenterology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki
3 Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo, Japan

For reprints and all correspondence: Yuji Heike, Department of Medical Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji Chuo-ku, Tokyo 104-0045, Japan. E-mail: yheike{at}ncc.go.jp

Received April 16, 2009; accepted August 10, 2009

Objective: Chemotherapy and immunotherapy often seem to contradict each other. However, recent reports suggested that the anticancer effects in some chemotherapeutic agents were concerned with immune response. This study was designed to evaluate the immunological reaction by gemcitabine for future clinical trial of combination therapy with gemcitabine and cancer vaccines.

Methods: We evaluated several immunological parameters in patients with advanced pancreatic cancer who received a conventional dose of gemcitabine for 2 months. Twenty-eight patients with metastasis or locally advanced tumor, including 18 gemcitabine-naïve and 10 with a history of preceding gemcitabine treatment, were enrolled in this study. The patients received gemcitabine 1000 mg/m2 for 3 weeks, followed by 1 week of rest. We monitored the kinetics of lymphocytes, natural killer cells, monocytes, dendritic cells (DC), human leukocyte antigen (HLA)-multimer conjugated with CMV or WT1 peptide, and intracellular cytokine production of interferon-{gamma} and interleukin-4 by flow cytometry. The T cell receptor (TCR) repertoire was also analyzed.

Results: The absolute number and percentage of CD14+ monocytes and CD11c+ (myeloid) DC increased with gemcitabine treatment (P = 0.033 and P = 0.021). The percentage of CD123+ (plasmacytoid) DC also increased (P = 0.034), whereas no significant change was observed in other immune parameters, including multimer, intracellular cytokine production and TCR repertoire.

Conclusions: Our finding that gemcitabine treatment induced the proliferation of CD14+ monocytes and CD11c+ DC could support combination therapy with gemcitabine and specific immunotherapy such as peptide vaccination against pancreatic cancers.

Key Words: gemcitabine • dendritic cell • monocyte • pancreatic cancer • cancer vaccines


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