PMID- 19797418 OWN - NLM STAT- MEDLINE DCOM- 20100106 LR - 20221207 IS - 1465-3621 (Electronic) IS - 0368-2811 (Linking) VI - 39 IP - 12 DP - 2009 Dec TI - Regular dose of gemcitabine induces an increase in CD14+ monocytes and CD11c+ dendritic cells in patients with advanced pancreatic cancer. PG - 797-806 LID - 10.1093/jjco/hyp112 [doi] AB - 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-naive and 10 with a history of preceding gemcitabine treatment, were enrolled in this study. The patients received gemcitabine 1000 mg/m(2) 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. FAU - Soeda, Atsuko AU - Soeda A AD - Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan. FAU - Morita-Hoshi, Yuriko AU - Morita-Hoshi Y FAU - Makiyama, Hiroaki AU - Makiyama H FAU - Morizane, Chigusa AU - Morizane C FAU - Ueno, Hideki AU - Ueno H FAU - Ikeda, Masafumi AU - Ikeda M FAU - Okusaka, Takuji AU - Okusaka T FAU - Yamagata, Shizuka AU - Yamagata S FAU - Takahashi, Noriko AU - Takahashi N FAU - Hyodo, Ichinosuke AU - Hyodo I FAU - Takaue, Yoichi AU - Takaue Y FAU - Heike, Yuji AU - Heike Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20091001 PL - England TA - Jpn J Clin Oncol JT - Japanese journal of clinical oncology JID - 0313225 RN - 0 (CD11c Antigen) RN - 0 (Cancer Vaccines) RN - 0 (Lipopolysaccharide Receptors) RN - 0W860991D6 (Deoxycytidine) RN - 207137-56-2 (Interleukin-4) RN - 82115-62-6 (Interferon-gamma) RN - 0 (Gemcitabine) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - CD11c Antigen/immunology MH - CD8-Positive T-Lymphocytes/immunology MH - *Cancer Vaccines/analysis/immunology MH - Combined Modality Therapy MH - Dendritic Cells/immunology MH - Deoxycytidine/*analogs & derivatives/pharmacology/therapeutic use MH - Female MH - Humans MH - Immunotherapy MH - Interferon-gamma/immunology/pharmacology MH - Interleukin-4/immunology MH - Killer Cells, Natural MH - Lipopolysaccharide Receptors/immunology MH - Lymphocyte Activation/immunology MH - Male MH - Middle Aged MH - Monocytes/*immunology MH - Pancreatic Neoplasms/cerebrospinal fluid/*immunology/microbiology MH - Gemcitabine EDAT- 2009/10/03 06:00 MHDA- 2010/01/07 06:00 CRDT- 2009/10/03 06:00 PHST- 2009/10/03 06:00 [entrez] PHST- 2009/10/03 06:00 [pubmed] PHST- 2010/01/07 06:00 [medline] AID - hyp112 [pii] AID - 10.1093/jjco/hyp112 [doi] PST - ppublish SO - Jpn J Clin Oncol. 2009 Dec;39(12):797-806. doi: 10.1093/jjco/hyp112. Epub 2009 Oct 1.