AIM:To investigate the prognostic role of invariant natural killer T(iNKT) cells and antibody-dependent cell-mediated cytotoxicity(ADCC) in wild type KRAS metastatic colorectal cancer(mC RC) patients treated with cetu...AIM:To investigate the prognostic role of invariant natural killer T(iNKT) cells and antibody-dependent cell-mediated cytotoxicity(ADCC) in wild type KRAS metastatic colorectal cancer(mC RC) patients treated with cetuximab.METHODS: Forty-one KRAS wt mC RC patients,treated with cetuximab and irinotecan-based chemotherapy in Ⅱ and Ⅲ lines were analyzed. Genotyping of single nucleotide polymorphism(SNP)s in the FCGR2A,FCGR3A and in the 3' untranslated regions of KRAS and mutational analysis for KRAS,BRAF and NRAS genes was determined either by sequencing or allelic discrimination assays. Enriched NK cells were obtained from lymphoprepperipheral blood mononuclear cell and iN KT cells were defined by co-expression of CD3,TCRVα24,TCRVβ11. ADCC was evaluated as ex vivo NK-dependent activity,measuring lactate dehydrogenase release.RESULTS: At basal,mCRC patients performing ADCC activity above the median level(71%) showed an improved overall survival(OS) compared to patients with ADCC below(median 16 vs 8 mo;P=0.026). We did not find any significant correlation of iN KT cells with OS(P=0.19),albeit we observed a trend to a longer survival after 10 mo in patients with iN KT above median basal level(0.382 cells/microliter). Correlation of OS and progression-free survival(PFS) with interesting SNPs involved in ADCC ability revealed not to be significant. Patients carrying alleles both with A in FCGR2 A and TT in FCGR3A presented a trend of longer PFS(median 9 vs 5 mo;P=0.064). Chemotherapy impacted both iN KT cells and ADCC activity. Their prognostic values get lost when we analysed them after 2 and 4 mo of treatment.CONCLUSION: Our results suggest a link between iN KT cells,basal ADCC activity,genotypes in FCGR2A and FCGR3A,and efficacy of cetuximab in KRAS wt mC RC patients.展开更多
Objective:To delineate immunomodulatory role of histamine on antibody generation pr of ile in rabbit in the present dose-dependent histamine study.Methods:The cohort comprised of three groups(Ⅲ,ⅣandⅤ),containing si...Objective:To delineate immunomodulatory role of histamine on antibody generation pr of ile in rabbit in the present dose-dependent histamine study.Methods:The cohort comprised of three groups(Ⅲ,ⅣandⅤ),containing six rabbits each,and received subcutaneous histamine 50μg/kg×bis in die(b.i.d.),100μg/kg×b.i.d.and 200μg/kg X b.i.d.,respectively for 10 days (starting from the 1st day).They were subsequently immunized on the 3rd day with intravenous injection of sheep blood cell(SRBC)(1×10 cells/mL).GroupⅡ(positive control)(n=6) received vehicle(sterile distilled water) and immunized at day 3 similarly while groupⅠ(negative control) (n=6) remained non-immunized and received only vehicle.All experimentations were performed in triplicate.Blood samples were collected on pre-immunization(pre-I)(day 0),as well as on days 7-,14-,21-,28- and 58- post-immunization(post-I).Immunological parameters[total immunoglobulins(Igs),IgM and IgG]were analyzed by enzyme linked immunosorbent assay (ELISA) technique.Results:Histamine could influence a detectable antibody response to SRBC as early as day 7-post-I,which lasted until day 58- post-I.The results were found statistically significant(P【 0.05).Conclusions:Our results provide evidence that histamine has a short-term effect on antibody generation(until its presence in the body),and the antibody generation titer in vivo were affected by the concentration of histamine.展开更多
Children with Coronavirus Disease 2019(COVID-19) were reported to show milder symptoms and better prognosis than their adult counterparts, but the difference of immune response against SARS-CoV-2 between children and ...Children with Coronavirus Disease 2019(COVID-19) were reported to show milder symptoms and better prognosis than their adult counterparts, but the difference of immune response against SARS-CoV-2 between children and adults hasn’t been reported. Therefore we initiated this study to figure out the features of immune response in children with COVID-19.Sera and whole blood cells from 19 children with COVID-19 during different phases after disease onset were collected.The cytokine concentrations, SARS-CoV-2 S-RBD or N-specific antibodies and T cell immune responses were detected respectively. In children with COVID-19, only 3 of 12 cytokines were increased in acute sera, including interferon(IFN)-cinduced protein 10(IP10), interleukin(IL)-10 and IL-16. We observed an increase in T helper(Th)-2 cells and a suppression in regulatory T cells(Treg) in patients during acute phase, but no significant response was found in the IFN-cproducing or tumor necrosis factor(TNF)-a-producing CD8?T cells in patients. S-RBD and N IgM showed an early induction, while S-RBD and N IgG were prominently induced later in convalescent phase. Potent S-RBD IgA response was observed but N IgA seemed to be inconspicuous. Children with COVID-19 displayed an immunophenotype that is less inflammatory than adults, including unremarkable cytokine elevation, moderate CD4?T cell response and inactive CD8?T cell response, but their humoral immunity against SARS-CoV-2 were as strong as adults. Our finding presented immunological characteristics of children with COVID-19 and might give some clues as to why children develop less severe disease than adults.展开更多
The role of anti-tumor immune responses in oncolytic adenoviral therapy has not been well studied due to lack of efficacious tu- mor model in immunocompetent mice.Here,we evaluated the contributions of immune componen...The role of anti-tumor immune responses in oncolytic adenoviral therapy has not been well studied due to lack of efficacious tu- mor model in immunocompetent mice.Here,we evaluated the contributions of immune components to the therapeutic effects of oncolytic adenoviruse in an immunocompetent murine tumor model permissive for infection and replication of adenovirus.We found that CD8+T cells were critical mediator for antitumor efficacy by oncolytic adenovirus.Intratumoral viral therapy induced intensive infiltration of CD8+T cells in tumor,increased tumor-specific IFN-?(interferon-?)production and CTL(cytotoxic T lymphocyte)activity of lymphocytes,and generated a long-term tumor-specific immune memory.Boosting CD8+T cell responses by agonistic anti-4-1BB(cluster differentiation 137,CD137)antibody showed synergistic anticancer effects with oncolytic viro- therapy.Our results provide insight into antitumor mechanisms of oncolytic adenovirus in addition to their direct oncolytic effect.展开更多
基金the Fondazione Veronesi that granted Daniela Vivenza and Martino Monteverde with PostDoctoral Fellowship Veronesithe Fondazione Cassa Risparmio of Cuneo for partially supporting the study
文摘AIM:To investigate the prognostic role of invariant natural killer T(iNKT) cells and antibody-dependent cell-mediated cytotoxicity(ADCC) in wild type KRAS metastatic colorectal cancer(mC RC) patients treated with cetuximab.METHODS: Forty-one KRAS wt mC RC patients,treated with cetuximab and irinotecan-based chemotherapy in Ⅱ and Ⅲ lines were analyzed. Genotyping of single nucleotide polymorphism(SNP)s in the FCGR2A,FCGR3A and in the 3' untranslated regions of KRAS and mutational analysis for KRAS,BRAF and NRAS genes was determined either by sequencing or allelic discrimination assays. Enriched NK cells were obtained from lymphoprepperipheral blood mononuclear cell and iN KT cells were defined by co-expression of CD3,TCRVα24,TCRVβ11. ADCC was evaluated as ex vivo NK-dependent activity,measuring lactate dehydrogenase release.RESULTS: At basal,mCRC patients performing ADCC activity above the median level(71%) showed an improved overall survival(OS) compared to patients with ADCC below(median 16 vs 8 mo;P=0.026). We did not find any significant correlation of iN KT cells with OS(P=0.19),albeit we observed a trend to a longer survival after 10 mo in patients with iN KT above median basal level(0.382 cells/microliter). Correlation of OS and progression-free survival(PFS) with interesting SNPs involved in ADCC ability revealed not to be significant. Patients carrying alleles both with A in FCGR2 A and TT in FCGR3A presented a trend of longer PFS(median 9 vs 5 mo;P=0.064). Chemotherapy impacted both iN KT cells and ADCC activity. Their prognostic values get lost when we analysed them after 2 and 4 mo of treatment.CONCLUSION: Our results suggest a link between iN KT cells,basal ADCC activity,genotypes in FCGR2A and FCGR3A,and efficacy of cetuximab in KRAS wt mC RC patients.
基金University Grants Commission, New Delhi,India for providing UGC Fellowship[UGC letter DON F.19-33/2006(CU)]M.Shahid is grateful to Department of Science & Technology,Ministry of Science & Technology,Government of India for awarding"Young Scientist Project Award"(FT/SR-L-111/2006)
文摘Objective:To delineate immunomodulatory role of histamine on antibody generation pr of ile in rabbit in the present dose-dependent histamine study.Methods:The cohort comprised of three groups(Ⅲ,ⅣandⅤ),containing six rabbits each,and received subcutaneous histamine 50μg/kg×bis in die(b.i.d.),100μg/kg×b.i.d.and 200μg/kg X b.i.d.,respectively for 10 days (starting from the 1st day).They were subsequently immunized on the 3rd day with intravenous injection of sheep blood cell(SRBC)(1×10 cells/mL).GroupⅡ(positive control)(n=6) received vehicle(sterile distilled water) and immunized at day 3 similarly while groupⅠ(negative control) (n=6) remained non-immunized and received only vehicle.All experimentations were performed in triplicate.Blood samples were collected on pre-immunization(pre-I)(day 0),as well as on days 7-,14-,21-,28- and 58- post-immunization(post-I).Immunological parameters[total immunoglobulins(Igs),IgM and IgG]were analyzed by enzyme linked immunosorbent assay (ELISA) technique.Results:Histamine could influence a detectable antibody response to SRBC as early as day 7-post-I,which lasted until day 58- post-I.The results were found statistically significant(P【 0.05).Conclusions:Our results provide evidence that histamine has a short-term effect on antibody generation(until its presence in the body),and the antibody generation titer in vivo were affected by the concentration of histamine.
基金supported by grants specific for Coronavirus Disease 2019 from the Children’s Hospital of Fudan University (Grant No. EKXGZX006)。
文摘Children with Coronavirus Disease 2019(COVID-19) were reported to show milder symptoms and better prognosis than their adult counterparts, but the difference of immune response against SARS-CoV-2 between children and adults hasn’t been reported. Therefore we initiated this study to figure out the features of immune response in children with COVID-19.Sera and whole blood cells from 19 children with COVID-19 during different phases after disease onset were collected.The cytokine concentrations, SARS-CoV-2 S-RBD or N-specific antibodies and T cell immune responses were detected respectively. In children with COVID-19, only 3 of 12 cytokines were increased in acute sera, including interferon(IFN)-cinduced protein 10(IP10), interleukin(IL)-10 and IL-16. We observed an increase in T helper(Th)-2 cells and a suppression in regulatory T cells(Treg) in patients during acute phase, but no significant response was found in the IFN-cproducing or tumor necrosis factor(TNF)-a-producing CD8?T cells in patients. S-RBD and N IgM showed an early induction, while S-RBD and N IgG were prominently induced later in convalescent phase. Potent S-RBD IgA response was observed but N IgA seemed to be inconspicuous. Children with COVID-19 displayed an immunophenotype that is less inflammatory than adults, including unremarkable cytokine elevation, moderate CD4?T cell response and inactive CD8?T cell response, but their humoral immunity against SARS-CoV-2 were as strong as adults. Our finding presented immunological characteristics of children with COVID-19 and might give some clues as to why children develop less severe disease than adults.
基金supported by the National Natural Science Foundation of China(30771968 and 91029719)
文摘The role of anti-tumor immune responses in oncolytic adenoviral therapy has not been well studied due to lack of efficacious tu- mor model in immunocompetent mice.Here,we evaluated the contributions of immune components to the therapeutic effects of oncolytic adenoviruse in an immunocompetent murine tumor model permissive for infection and replication of adenovirus.We found that CD8+T cells were critical mediator for antitumor efficacy by oncolytic adenovirus.Intratumoral viral therapy induced intensive infiltration of CD8+T cells in tumor,increased tumor-specific IFN-?(interferon-?)production and CTL(cytotoxic T lymphocyte)activity of lymphocytes,and generated a long-term tumor-specific immune memory.Boosting CD8+T cell responses by agonistic anti-4-1BB(cluster differentiation 137,CD137)antibody showed synergistic anticancer effects with oncolytic viro- therapy.Our results provide insight into antitumor mechanisms of oncolytic adenovirus in addition to their direct oncolytic effect.
