Regular dose of gemcitabine induces an increase in CD14+ monocytes and CD11c+ dendritic cells in patients with advanced pancreatic cancer.
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/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.
Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
Atsuko
A
Soeda
Yuriko
Y
Morita-Hoshi
Hiroaki
H
Makiyama
Chigusa
C
Morizane
Hideki
H
Ueno
Masafumi
M
Ikeda
Takuji
T
Okusaka
Shizuka
S
Yamagata
Noriko
N
Takahashi
Ichinosuke
I
Hyodo
Yoichi
Y
Takaue
Yuji
Y
Heike
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D039521:CD11c Antigen / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000032:analysis / Q000276:immunology; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D015847:Interleukin-4 / Q000276:immunology; D007694:Killer Cells, Natural; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D010190:Pancreatic Neoplasms / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000382:microbiology; D000093542:Gemcitabine
D039521:CD11c Antigen; D019496:Cancer Vaccines; D018950:Lipopolysaccharide Receptors; D003841:Deoxycytidine; D015847:Interleukin-4; D007371:Interferon-gamma; D000093542:Gemcitabine