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WebPage:
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         headline:Immunological effects of adjuvants in subsets of antigen presenting cells of cancer patients undergoing chemotherapy
         description:We have previously shown that HCC patients and healthy subjects are equally responsive to a RNAdjuvant®, a novel TLR-7/8/RIG-I agonist based on noncoding RNA developed by CureVac, by an ex vivo evaluation. However, the immunological effect of adjuvants on immune cells from cancer patients undergoing chemotherapy remains to be demonstrated. Different adjuvants currently used in cancer vaccine clinical trials were evaluated in the present study on immune cells from cancer patients before and after chemotherapy in an ex vivo setting. PBMCs were obtained from 4 healthy volunteers and 23 patients affected by either colon (OMA) or lung cancer (OT). The effect of CpG, Poly I:C, Imiquimod and RNA-based adjuvant (RNAdjuvant®) was assessed using a multiparametric approach to analyze network dynamics of early immune responses. Evaluation of CD80, CD86 and HLA-DR expression as well as the downstream effect on CD4+ T cell phenotyping was performed by flow cytometry; cytokine and chemokine production was evaluated by Bio-Plex ProTM. Treatment with RNAdjuvant® induced the strongest response in cancer patients in terms of activation of innate and adoptive immunity. Indeed, CD80, CD86 and HLA-DR expression was found upregulated in circulating dendritic cells, which promoted a CD4+ T cell differentiation towards an effector phenotype. RNAdjuvant® was the only one to induce most of the cytokines/chemokines tested with a pronounced Th1 cytokine pattern. According to the different parameters evaluated in the study, no clear cut difference in immune response to adjuvants was observed between healthy subjects and cancer patients. Moreover, in the latter group, the chemotherapy treatment did not consistently correlate to a significant altered response in the different parameters. The present study is the first analysis of immunological effects induced by adjuvants in cancer patients who undergo chemotherapy, who are enrolled in the currently ongoing cancer vaccine clinical trials. The results show that the RNAdjuvant® is a potent and Th1 driving adjuvant, compared to those tested in the present study. Most importantly, it is demonstrated that chemotherapy does not significantly impair the immune system, implying that cancer patients are likely to respond to a cancer vaccine even after a chemotherapy treatment.
         datePublished:2020-01-23T00:00:00Z
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            Adjuvant
            Colon cancer
            Lung cancer
            Immune-response
            Cancer vaccine
            Biomedicine
            general
            Medicine/Public Health
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                     address:
                        name:Laboratory of Cancer Immunoregulation, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
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                     address:
                        name:Laboratory of Cancer Immunoregulation, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
                        type:PostalAddress
                     type:Organization
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               name:Beatrice Cavalluzzo
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                     address:
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                     address:
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               name:Maria Lina Tornesello
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                     address:
                        name:Laboratory of Molecular Biology and Viral Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
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               name:Franco M. Buonaguro
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                     address:
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               name:Maria Tagliamonte
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                     address:
                        name:Laboratory of Cancer Immunoregulation, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
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ScholarlyArticle:
      headline:Immunological effects of adjuvants in subsets of antigen presenting cells of cancer patients undergoing chemotherapy
      description:We have previously shown that HCC patients and healthy subjects are equally responsive to a RNAdjuvant®, a novel TLR-7/8/RIG-I agonist based on noncoding RNA developed by CureVac, by an ex vivo evaluation. However, the immunological effect of adjuvants on immune cells from cancer patients undergoing chemotherapy remains to be demonstrated. Different adjuvants currently used in cancer vaccine clinical trials were evaluated in the present study on immune cells from cancer patients before and after chemotherapy in an ex vivo setting. PBMCs were obtained from 4 healthy volunteers and 23 patients affected by either colon (OMA) or lung cancer (OT). The effect of CpG, Poly I:C, Imiquimod and RNA-based adjuvant (RNAdjuvant®) was assessed using a multiparametric approach to analyze network dynamics of early immune responses. Evaluation of CD80, CD86 and HLA-DR expression as well as the downstream effect on CD4+ T cell phenotyping was performed by flow cytometry; cytokine and chemokine production was evaluated by Bio-Plex ProTM. Treatment with RNAdjuvant® induced the strongest response in cancer patients in terms of activation of innate and adoptive immunity. Indeed, CD80, CD86 and HLA-DR expression was found upregulated in circulating dendritic cells, which promoted a CD4+ T cell differentiation towards an effector phenotype. RNAdjuvant® was the only one to induce most of the cytokines/chemokines tested with a pronounced Th1 cytokine pattern. According to the different parameters evaluated in the study, no clear cut difference in immune response to adjuvants was observed between healthy subjects and cancer patients. Moreover, in the latter group, the chemotherapy treatment did not consistently correlate to a significant altered response in the different parameters. The present study is the first analysis of immunological effects induced by adjuvants in cancer patients who undergo chemotherapy, who are enrolled in the currently ongoing cancer vaccine clinical trials. The results show that the RNAdjuvant® is a potent and Th1 driving adjuvant, compared to those tested in the present study. Most importantly, it is demonstrated that chemotherapy does not significantly impair the immune system, implying that cancer patients are likely to respond to a cancer vaccine even after a chemotherapy treatment.
      datePublished:2020-01-23T00:00:00Z
      dateModified:2020-01-23T00:00:00Z
      pageStart:1
      pageEnd:17
      license:http://creativecommons.org/publicdomain/zero/1.0/
      sameAs:https://doi.org/10.1186/s12967-020-02218-x
      keywords:
         Adjuvant
         Colon cancer
         Lung cancer
         Immune-response
         Cancer vaccine
         Biomedicine
         general
         Medicine/Public Health
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         name:Journal of Translational Medicine
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            1479-5876
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            name:Angela Mauriello
            affiliation:
                  name:Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”
                  address:
                     name:Laboratory of Cancer Immunoregulation, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
                     type:PostalAddress
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            name:Carmen Manolio
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            name:Beatrice Cavalluzzo
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                  name:Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”
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                  address:
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            name:Maria Lina Tornesello
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                     name:Laboratory of Cancer Immunoregulation, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
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      name:Università della Campania “Luigi Vanvitelli”
      address:
         name:Environmental, Biological and Pharmaceutical Science and Technology Dept, Università della Campania “Luigi Vanvitelli”, Caserta, Italy
         type:PostalAddress
      name:Università della Campania “Luigi Vanvitelli”
      address:
         name:Environmental, Biological and Pharmaceutical Science and Technology Dept, Università della Campania “Luigi Vanvitelli”, Caserta, Italy
         type:PostalAddress
      name:Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”
      address:
         name:Laboratory of Molecular Biology and Viral Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
         type:PostalAddress
      name:Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”
      address:
         name:Laboratory of Molecular Biology and Viral Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
         type:PostalAddress
      name:Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”
      address:
         name:Laboratory of Cancer Immunoregulation, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
         type:PostalAddress
      name:Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”
      address:
         name:Laboratory of Cancer Immunoregulation, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
         type:PostalAddress
ImageObject:
      url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
Person:
      name:Angela Mauriello
      affiliation:
            name:Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”
            address:
               name:Laboratory of Cancer Immunoregulation, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
               type:PostalAddress
            type:Organization
      name:Carmen Manolio
      affiliation:
            name:Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”
            address:
               name:Laboratory of Cancer Immunoregulation, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
               type:PostalAddress
            type:Organization
      name:Beatrice Cavalluzzo
      affiliation:
            name:Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”
            address:
               name:Laboratory of Cancer Immunoregulation, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
               type:PostalAddress
            type:Organization
      name:Antonio Avallone
      affiliation:
            name:Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”
            address:
               name:GI Medical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
               type:PostalAddress
            type:Organization
      name:Marco Borrelli
      affiliation:
            name:Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”
            address:
               name:Laboratory of Cancer Immunoregulation, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
               type:PostalAddress
            type:Organization
      name:Alessandro Morabito
      affiliation:
            name:Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”
            address:
               name:Thoracic Medical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
               type:PostalAddress
            type:Organization
      name:Emanuele Iovine
      affiliation:
            name:Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”
            address:
               name:Thoracic Medical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
               type:PostalAddress
            type:Organization
      name:Angela Chambery
      affiliation:
            name:Università della Campania “Luigi Vanvitelli”
            address:
               name:Environmental, Biological and Pharmaceutical Science and Technology Dept, Università della Campania “Luigi Vanvitelli”, Caserta, Italy
               type:PostalAddress
            type:Organization
      name:Rosita Russo
      affiliation:
            name:Università della Campania “Luigi Vanvitelli”
            address:
               name:Environmental, Biological and Pharmaceutical Science and Technology Dept, Università della Campania “Luigi Vanvitelli”, Caserta, Italy
               type:PostalAddress
            type:Organization
      name:Maria Lina Tornesello
      affiliation:
            name:Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”
            address:
               name:Laboratory of Molecular Biology and Viral Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
               type:PostalAddress
            type:Organization
      name:Franco M. Buonaguro
      affiliation:
            name:Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”
            address:
               name:Laboratory of Molecular Biology and Viral Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
               type:PostalAddress
            type:Organization
      name:Maria Tagliamonte
      affiliation:
            name:Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”
            address:
               name:Laboratory of Cancer Immunoregulation, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Luigi Buonaguro
      url:http://orcid.org/0000-0002-6380-7114
      affiliation:
            name:Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”
            address:
               name:Laboratory of Cancer Immunoregulation, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Laboratory of Cancer Immunoregulation, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
      name:Laboratory of Cancer Immunoregulation, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
      name:Laboratory of Cancer Immunoregulation, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
      name:GI Medical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
      name:Laboratory of Cancer Immunoregulation, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
      name:Thoracic Medical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
      name:Thoracic Medical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
      name:Environmental, Biological and Pharmaceutical Science and Technology Dept, Università della Campania “Luigi Vanvitelli”, Caserta, Italy
      name:Environmental, Biological and Pharmaceutical Science and Technology Dept, Università della Campania “Luigi Vanvitelli”, Caserta, Italy
      name:Laboratory of Molecular Biology and Viral Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
      name:Laboratory of Molecular Biology and Viral Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
      name:Laboratory of Cancer Immunoregulation, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy
      name:Laboratory of Cancer Immunoregulation, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS “Fondazione Pascale”, Naples, Italy

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