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| 1 | Immunotherapy for colorectal cancer显示文摘The incidence of colorectal cancer(CRC)is on the rise,and the prognosis for patients with recurrent or metastatic disease is extremely poor.Although chemotherapy and radiation therapy can improve survival rates,it is imperative to integrate alternative strategies such as immunotherapy to improve outcomes for patients with advanced CRC.In this review,we will discuss the effect of immunotherapy for inducing cytotoxic T lymphocytes and the major immunotherapeutic approaches for CRC that are currently in clinical trials,including peptide vaccines,dendritic cell-based cancer vaccines,whole tumor cell vaccines,viral vector-based cancer vaccines,adoptive cell transfer therapy,antibody-based cancer immunotherapy,and cytokine therapy.The possibility of combination therapies will also be discussed along with the challenges presented by tumor escape mechanisms. | Shigeo Koido Toshifumi Ohkusa Sadamu Homma Yoshihisa Namiki Kazuki Takakura Keisuke Saito Zensho Ito Hiroko Kobayashi Mikio Kajihara Kan Uchiyama Seiji Arihiro Hiroshi Arakawa Masato Okamoto Jianlin Gong Hisao Tajiri | 2013 | World Journal of Gastroenterology2013，19，46： | 11 |
| 2 | Advances in inducing adaptive immunity using cell-based cancer vaccines: clinical applications in pancreatic cancer显示文摘The incidence of pancreatic ductal adenocarcinoma(PDA) is on the rise, and the prognosis is extremely poor because PDA is highly aggressive and notoriously difficult to treat. Although gemcitabine- or 5-fluorouracil-based chemotherapy is typically offered as a standard of care, most patients do not survive longer than 1 year. Therefore, the development of alternative therapeutic approaches for patients with PDA is imperative. As PDA cells express numerous tumor-associated antigens that are suitable vaccine targets, one promising treatment approach is cancer vaccines. During the last few decades, cell-based cancer vaccines have offered encouraging results in preclinical studies. Cell-based cancer vaccines are mainly generated by presenting whole tumor cells or dendritic cells to cells of the immune system. In particular, several clinical trials have explored cell-based cancer vaccines as a promising therapeutic approach for patients with PDA. Moreover, chemotherapy and cancer vaccines can synergize to result in increased efficacies in patients with PDA. In this review, we will discuss both the effect of cell-based cancer vaccines and advances in terms of future strategies of cancer vaccines for the treatment of PDA patients. | Mikio Kajihara Kazuki Takakura Tomoya Kanai Zensho Ito Yoshihiro Matsumoto Shigetaka Shimodaira Masato Okamoto Toshifumi Ohkusa Shigeo Koido | 2016 | World Journal of Gastroenterology2016，22，18： | 4 |
| 3 | Fusions between dendritic cells and whole tumor cells as anticancer vaccines显示文摘 | Shigeo Koido Sadamu Homma Masato Okamoto Yoshihisa Namiki Kazuki Takakura Kan Uchiyama Mikio Kajihara Seiji Arihiro Hiroo Imazu Hiroshi Arakawa Shin Kan Hideo Komita Masaki Ito Toshifumi Ohkusa Jianlin Gong Hisao Tajiri | 2013 | OncoImmunology2013，，： | 3 |
| 4 | Impact of dendritic cell vaccines pulsed with Wilms’ tumour-1 peptide antigen on the survival of patients with advanced non-small cell lung cancers显示文摘 | Hidenori Takahashi Masato Okamoto Shigetaka Shimodaira Shun-ichi Tsujitani Masaki Nagaya Takefumi Ishidao Junji Kishimoto Yoshikazu Yonemitsu | 2012 | European Journal of Cancer2012，，： | 3 |
| 5 | Dendritic cell-based cancer immunotherapy for colorectal cancer显示文摘Colorectal cancer(CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the prognosis is extremely poor. The optimal sequence of therapy remains unknown. Therefore, alternative strategies, such as immunotherapy, are needed for patients with advanced CRC. This review summarizes evidence from dendritic cell-based cancer immunotherapy strategies that are currently in clinical trials. In addition, we discuss the possibility of antitumor immune responses through immunoinhibitory PD-1/PD-L1 pathway blockade in CRC patients. | Mikio Kajihara Kazuki Takakura Tomoya Kanai Zensho Ito Keisuke Saito Shinichiro Takami Shigetaka Shimodaira Masato Okamoto Toshifumi Ohkusa Shigeo Koido | 2016 | World Journal of Gastroenterology2016，22，17： | 3 |
| 6 | Dendritic cell-based vaccine for pancreatic cancer in Japan显示文摘'Vaccell' is a dendritic cell(DC)-based cancer vaccine which has been established in Japan. The DCs play central roles in deciding the direction of host immune reactions as well as antigen presentation. We have demonstrated that DCs treated with a streptococcal immune adjuvant OK-432, produce interleukin-12, induce Th1-dominant state, and elicit anti-tumor effects, more powerful than those treated with the known DCmaturating factors. We therefore decided to mature DCs by the OK-432 for making an effective DC vaccine, Vaccell. The 255 patients with inoperable pancreatic cancer who received standard chemotherapy combined with DC vaccines, were analyzed retrospectively. Survival time of the patients with positive delayed type hypersensitivity(DTH) skin reaction was significantly prolonged as compared with that of the patients with negative DTH. The findings strongly suggest that there may be 'Responders' for the DC vaccine in advanced pancreatic cancer patients. We next conducted a smallscale prospective clinical study. In this trial, we pulsed HLA class Ⅱ-restricted WT1 peptide(WT1-Ⅱ) in addition to HLA class Ⅰ-restricted peptide(WT1-Ⅰ) into the DCs. Survival of the patients received WT1-Ⅰ and-Ⅱ pulsed DC vaccine was significantly extended as compared to that of the patients received DCs pulsed with WT1-Ⅰ or WT1-Ⅱ alone. Furthermore, WT1-specific DTH positive patients showed significantly improved the overall survival as well as progressionfree survival as compared to the DTH negative patients. The activation of antigen-specific immune responses by DC vaccine in combination with standard chemotherapy may be associated with a good clinical outcome in advanced pancreatic cancer. We are now planning a pivotal study of the Vaccell in appropriate protocols in Japan. | Masato Okamoto Masanori Kobayashi Yoshikazu Yonemitsu Shigeo Koido Sadamu Homma | 2016 | World Journal of Gastrointestinal Pharmacology and Therapeutics2016，7，1： | 2 |
| 7 | Production of corticotropin-releasing factor and urocortin from human monocyte-derived dendritic cells is stimulated by commensal bacteria in intestine显示文摘AIM:To examine whether commensal bacteria are a contributing cause of stress-related mucosal inflammation.METHODS:Human peripheral blood monocyte-deriveddendritic cells(MoDCs)were stimulated by commensal bacterial strains,including Escherichia coli,Clostridium clostridioforme,Bacteroides vulgatus(B.vulgatus),Fusobacterium varium(F.varium),and Lactobacillus delbrueckii subsp.bulgaricus.After incubation,corticotropin-releasing factor(CRF)and urocortin 1(UCN1)mRNA in the cells was examined by real-time reverse transcription polymerase chain reaction.Supernatants from the cells were tested for CRF and UCN1 using an enzyme-linked immunosorbent assay.RESULTS:Both CRF and UCN1 were significantly augmented by B.vulgatus and F.varium at both the mRNA and protein levels.In particular,B.vulgatus stimulated human MoDCs,resulting in extremely high levels of CRF and UCN1.CONCLUSION:Stimulation of MoDCs by B.vulgatus and F.varium may be associated with CRF/UCN1-related intestinal disorders,such as irritable bowel syndrome and inflammatory bowel disease. | Shigeo Koido Toshifumi Ohkusa Shin Kan Kazuki Takakura Keisuke Saito Hideo Komita Zensho Ito Hiroko Kobayashi Shinichiro Takami Kan Uchiyama Hiroshi Arakawa Masaki Ito Masato Okamoto Mikio Kajihara Sadamu Homma Hisao Tajiri | 2014 | World Journal of Gastroenterology2014，20，39： | 2 |
| 8 | Adipocyte-Derived Plasma Protein, Adiponectin, Suppresses Lipid Accumulation and Class A Scavenger Receptor Expression in Human Monocyte-Derived Macrophages显示文摘 | Noriyuki Ouchi Shinji Kihara Yukio Arita Makoto Nishida Akifumi Matsuyama Yoshihisa Okamoto Masato Ishigami Hiroshi Kuriyama Ken Kishida Hitoshi Nishizawa Kikuko Hotta Masahiro Muraguchi Yasukazu Ohmoto Shizuya Yamashita Tohru Funahashi Yuji Matsuzawa | 2001 | Circulation: Journal of the American Heart Association2001，，8： | 2 |
| 9 | Chemoimmunotherapy targeting Wilms’ tumor 1 (WT1)-specific cytotoxic T lymphocyte and helper T cell responses for patients with pancreatic cancer显示文摘 | Shigeo Koido Sadamu Homma Masato Okamoto Kazuki Takakura Jianlin Gong Haruo Sugiyama Toshifumi Ohkusa Hisao Tajiri | 2014 | OncoImmunology2014，，10： | 2 |
| 10 | Prognostic factors related to add-on dendritic cell vaccines on patients with inoperable pancreatic cancer receiving chemotherapy: a multicenter analysis显示文摘 | Masanori Kobayashi Shigetaka Shimodaira Kazuhiro Nagai Masahiro Ogasawara Hidenori Takahashi Hirofumi Abe Mitsugu Tanii Masato Okamoto Sun-ichi Tsujitani Seiichi Yusa Takefumi Ishidao Junji Kishimoto Yuta Shibamoto Masaki Nagaya Yoshikazu Yonemitsu | 2014 | Cancer Immunology, Immunotherapy2014，，： | 2 |
| 11 | Adipocyte-Derived Plasma Protein, Adiponectin, Suppresses Lipid Accumulation and Class A Scavenger Receptor Expression in Human Monocyte-Derived Macrophages显示文摘 | Noriyuki Ouchi Shinji Kihara Yukio Arita Makoto Nishida Akifumi Matsuyama Yoshihisa Okamoto Masato Ishigami Hiroshi Kuriyama Ken Kishida Hitoshi Nishizawa Kikuko Hotta Masahiro Muraguchi Yasukazu Ohmoto Shizuya Yamashita Tohru Funahashi Yuji Matsuzawa | 2001 | Circulation: Journal of the American Heart Association2001，，8： | 2 |
| 12 | Immune?maximizing (IMAX) therapy for cancer: Combination of dendriticcell vaccine and intensity?modulated radiation显示文摘 | Yuta Shibamoto Masato Okamoto Masanori Kobayashi Shiho Ayakawa Hiromitsu Iwata Chikao Sugie Yoko Mitsuishi Hidenori Takahashi | 2013 | Molecular and Clinical Oncology2013，，： | 1 |
| 13 | Prognostic significance of plasma interleukin-6/-8 in pancreatic cancer patients receiving chemoimmunotherapy显示文摘AIM: To investigate the association of plasma levels of interleukin(IL)-6 and-8 with Wilms' tumor 1(WT1)-specific immune responses and clinical outcomes in patients with pancreatic ductal adenocarcinoma(PDA) treated with dendritic cells(DCs) pulsed with three types of major histocompatibility complex classⅠand Ⅱ-restricted WT1 peptides combined with chemotherapy.METHODS: During the entire treatment period, plasma levels of IL-6 and-8 were analyzed by ELISA. The induction of WT1-specific immune responses was assessed using the WT1 peptide-specific delayed-type hypersensitivity(DTH) test.RESULTS: Three of 7 patients displayed strong WT1-DTH reactions throughout long-term vaccination with significantly decreased levels of IL-6/-8 after vaccinations compared with the levels prior to treatment. Moreover, overall survival(OS) was significantly longer in PDA patients with low plasma IL-6 levels(< 2 pg/m L) after 5 vaccinations than in patients with high plasma IL-6 levels(≥ 2 pg/m L)(P = 0.025). After disease progression, WT1-DTH reactions decreased severely and were ultimately negative at the terminal stage of cancer. The decreased levels of IL-6/-8 observed throughout long-term vaccination were associated with WT1-specific DTH reactions and long-term OS.CONCLUSION: Prolonged low levels of plasma IL-6/-8 in PDA patients may be a prognostic marker for the clinical outcomes of chemoimmunotherapy. | Shintaro Tsukinaga Mikio Kajihara Kazuki Takakura Zensho Ito Tomoya Kanai Keisuke Saito Shinichiro Takami Hiroko Kobayashi Yoshihiro Matsumoto Shunichi Odahara Kan Uchiyama Hiroshi Arakawa Masato Okamoto Haruo Sugiyama Kazuki Sumiyama Toshifumi Ohkusa Shigeo Koido | 2015 | World Journal of Gastroenterology2015，21，39： | 1 |
| 14 | Growth inhibition and apoptosis by an active component of OK-432, a streptococcal agent, via Toll-like receptor 4 in human head and neck cancer cell lines显示文摘 | Tomoyuki Tano Masato Okamoto Shin Kan Koh-ichi Nakashiro Shigetaka Shimodaira Naomi Yamashita Yutaka Kawakami Hiroyuki Hamakawa | 2012 | Oral Oncology2012，，8： | 1 |
| 15 | Severe impairment of anti-cancer effect of lipoteichoic acid-related molecule isolated from a penicillinkilled Streptococcus pyogenes in toll-like receptor 4-deficient mice显示文摘 | Masato Okamoto Tetsuya Oshikawa | 2001 | International Immunopharmacology2001，1，： | 1 |
| 16 | Adipocyte-Derived Plasma Protein, Adiponectin, Suppresses Lipid Accumulation and Class A Scavenger Receptor Expression in Human Monocyte-Derived Macrophages显示文摘 | Noriyuki Ouchi Shinji Kihara Yukio Arita Makoto Nishida Akifumi Matsuyama Yoshihisa Okamoto Masato Ishigami Hiroshi Kuriyama Ken Kishida Hitoshi Nishizawa Kikuko Hotta Masahiro Muraguchi Yasukazu Ohmoto Shizuya Yamashita Tohru Funahashi Yuji Matsuzawa | 2001 | Circulation: Journal of the American Heart Association2001，，8： | 1 |
| 17 | Biological Effect of OK-432(Picibanil)and Possible Application to Dendritic Cell Therapy显示文摘 | Yoshiki Ryoma Yoichiro Moriya Masato Okamoto | 2004 | Anticancer Res2004，8，24： | 1 |
| 18 | Marked Genomic Heterogeneity and Frequent Mixed Infection of TT Virus Demonstrated by PCR with Primers from Coding and Noncoding Regions显示文摘 | Hiroaki Okamoto Masaharu Takahashi Tsutomu Nishizawa Masato Ukita Masako Fukuda Fumio Tsuda Yuzo Miyakawa Makoto Mayumi | 1999 | Virology1999，，2： | 1 |
| 19 | Adipocyte-Derived Plasma Protein, Adiponectin, Suppresses Lipid Accumulation and Class A Scavenger Receptor Expression in Human Monocyte-Derived Macrophages显示文摘 | Noriyuki Ouchi Shinji Kihara Yukio Arita Makoto Nishida Akifumi Matsuyama Yoshihisa Okamoto Masato Ishigami Hiroshi Kuriyama Ken Kishida Hitoshi Nishizawa Kikuko Hotta Masahiro Muraguchi Yasukazu Ohmoto Shizuya Yamashita Tohru Funahashi Yuji Matsuzawa | 2001 | Circulation: Journal of the American Heart Association2001，，8： | 1 |
| 20 | Strategies to improve the immunogenicity of anticancer vaccines based on dendritic cell/malignant cell fusions显示文摘 | shigeo koido Sadamu Homma Masato Okamoto Yoshihisa Namiki Kazuki Takakura Kan Uchiyama Mikio Kajihara Seiji Arihiro Hiroo Imazu Hiroshi Arakawa Shin Kan Hideo Komita Yuko Kamata Masaki Ito Toshifumi Ohkusa Jianlin Gong Hisao Tajiri | 2013 | OncoImmunology2013，，9： | 1 |
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