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Articles by Y Morita Hoshi
Total Records ( 2 ) for Y Morita Hoshi
  A Soeda , Y Morita Hoshi , H Makiyama , C Morizane , H Ueno , M Ikeda , T Okusaka , S Yamagata , N Takahashi , I Hyodo , Y Takaue and Y. Heike

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.


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- and interleukin-4 by flow cytometry. The T cell receptor (TCR) repertoire was also analyzed.


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.


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.

  A Soeda , Y Morita Hoshi , M Kaida , T Wakeda , Y Yamaki , Y Kojima , H Ueno , S Kondo , C Morizane , M Ikeda , T Okusaka and Y. Heike

The skin toxicity of vaccine therapy at injection sites is generally limited to Grades 1–2 due to the nature of their function. We experienced two cases of severe and prolonged local adverse effects in 25 patients following a Phase I study of gemcitabine and Wilms tumor-1 peptide vaccine mixed with incomplete Freund's adjuvant for inoperable pancreatic or biliary tract cancer. These patients requested to continue the treatment after the study period; however, in the course of compassionate use, they developed unacceptable local skin reactions and terminated their vaccine treatment. One patient (human leukocyte antigen, A0201, 3 mg) developed Grade 3 ulceration at the 10th vaccination and another (human leukocyte antigen, A2402, 1 mg) developed Grade 2 indulation and fibrosis at the 16th vaccination. Skin toxicity occurred at 6.4–8.4 months and continued for several months after the final vaccination during gemcitabine treatment. In these cases, activation or induction of Wilms tumor-1-specific T lymphocytes was not apparent in the peripheral blood despite their severe local reactions. Therefore, we need to monitor patients for late-onset, severe and long-lasting skin reactions at injection sites in Wilms tumor-1 cancer vaccine therapy, particularly for combination treatment with gemcitabine.

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