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 ...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.展开更多
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-b...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.展开更多
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 pro...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.展开更多
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 str...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.展开更多
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) treat...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.展开更多
The aim of the present study was to investigate the efficacy of the actual consuming n-3 PUFA for remission-maintenance in IBD patients. A questionnaire on the dietary habits of patients one month before hospitalizati...The aim of the present study was to investigate the efficacy of the actual consuming n-3 PUFA for remission-maintenance in IBD patients. A questionnaire on the dietary habits of patients one month before hospitalization (Q1) was completed by 24 patients with IBD (10 ulcerative colitis (UC) subjects and 14 Crohn’s disease (CD) subjects) treated at our hospital. We educated the study subjects about an n-3 PUFA diet, and a follow-up survey (Q2) was conducted 6 to 12 months after discharge. Disease activity was evaluated using the International Organization for the Study of Inflammatory Bowel Disease (IOIBD) score and/or the Crohn’s Disease Activity Index (CDAI) score for CD and the partial UCDAI score without endoscopic evaluation for UC. Q1 showed that the average n-3 and n-6 PUFA intakes were 1673 ± 1651 mg and 9146 ± 5217 mg, respectively, and the average n-3/n-6 ratio was 0.27 ± 0.31. In Q2, the intake of n-3 PUFA was significantly higher (3671 ± 1684 mg, p < 0.001), whereas the n-6 PUFA intake decreased significantly (5217 ± 1973 mg, p < 0.001) compared to those in Q1. As a consequence, the dietary n-3/ n-6 ratio was significantly increased (0.87 ± 0.60, p < 0.001). Maintenance of the remission rate was significantly higher in IBD patients who complied with the n-3 diet, and these patients maintained a dietary n-3/n-6 ratio of 0.432 or higher (17 of 23 cases;70.8%, p < 0.03) compared to that observed for IBD patients who did not comply with the diet. These results emphasize the importance of adjusting dietary PUFA and suggest that the n-3 diet may be effective in maintaining the remission of IBD.展开更多
基金Supported by Grants in Aid for Scientific Research(C)from the Japanese Ministry of Education,Culture,Sports,Science and Technology
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.
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.
基金Supported by Grants in Aid for Scientific Research (C) from the Japanese Ministry of Education, Culture, Sports, Science, and Technology.
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.
基金Supported by Grants-in-Aid for Scientific Research(C)from the Ministry of Education,Culture,Sports,Science,and Tech-nology of Japanthe Foundation for the Promotion of Can-cer Research and Mitsui Life Social Welfare Foundation
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.
基金Grants-in-Aid for Scientific Research(C)from the Ministry of Education,Culture,Sports,Science and Technology of Japan
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.
文摘The aim of the present study was to investigate the efficacy of the actual consuming n-3 PUFA for remission-maintenance in IBD patients. A questionnaire on the dietary habits of patients one month before hospitalization (Q1) was completed by 24 patients with IBD (10 ulcerative colitis (UC) subjects and 14 Crohn’s disease (CD) subjects) treated at our hospital. We educated the study subjects about an n-3 PUFA diet, and a follow-up survey (Q2) was conducted 6 to 12 months after discharge. Disease activity was evaluated using the International Organization for the Study of Inflammatory Bowel Disease (IOIBD) score and/or the Crohn’s Disease Activity Index (CDAI) score for CD and the partial UCDAI score without endoscopic evaluation for UC. Q1 showed that the average n-3 and n-6 PUFA intakes were 1673 ± 1651 mg and 9146 ± 5217 mg, respectively, and the average n-3/n-6 ratio was 0.27 ± 0.31. In Q2, the intake of n-3 PUFA was significantly higher (3671 ± 1684 mg, p < 0.001), whereas the n-6 PUFA intake decreased significantly (5217 ± 1973 mg, p < 0.001) compared to those in Q1. As a consequence, the dietary n-3/ n-6 ratio was significantly increased (0.87 ± 0.60, p < 0.001). Maintenance of the remission rate was significantly higher in IBD patients who complied with the n-3 diet, and these patients maintained a dietary n-3/n-6 ratio of 0.432 or higher (17 of 23 cases;70.8%, p < 0.03) compared to that observed for IBD patients who did not comply with the diet. These results emphasize the importance of adjusting dietary PUFA and suggest that the n-3 diet may be effective in maintaining the remission of IBD.