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Immunological effects of adjuvants in subsets of antigen presenting cells of cancer patients undergoing chemotherapy

BACKGROUND: 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 patie...

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Autores principales: Mauriello, Angela, Manolio, Carmen, Cavalluzzo, Beatrice, Avallone, Antonio, Borrelli, Marco, Morabito, Alessandro, Iovine, Emanuele, Chambery, Angela, Russo, Rosita, Tornesello, Maria Lina, Buonaguro, Franco M., Tagliamonte, Maria, Buonaguro, Luigi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977281/
https://www.ncbi.nlm.nih.gov/pubmed/31973714
http://dx.doi.org/10.1186/s12967-020-02218-x
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author Mauriello, Angela
Manolio, Carmen
Cavalluzzo, Beatrice
Avallone, Antonio
Borrelli, Marco
Morabito, Alessandro
Iovine, Emanuele
Chambery, Angela
Russo, Rosita
Tornesello, Maria Lina
Buonaguro, Franco M.
Tagliamonte, Maria
Buonaguro, Luigi
author_facet Mauriello, Angela
Manolio, Carmen
Cavalluzzo, Beatrice
Avallone, Antonio
Borrelli, Marco
Morabito, Alessandro
Iovine, Emanuele
Chambery, Angela
Russo, Rosita
Tornesello, Maria Lina
Buonaguro, Franco M.
Tagliamonte, Maria
Buonaguro, Luigi
author_sort Mauriello, Angela
collection PubMed
description BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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spelling pubmed-69772812020-01-28 Immunological effects of adjuvants in subsets of antigen presenting cells of cancer patients undergoing chemotherapy Mauriello, Angela Manolio, Carmen Cavalluzzo, Beatrice Avallone, Antonio Borrelli, Marco Morabito, Alessandro Iovine, Emanuele Chambery, Angela Russo, Rosita Tornesello, Maria Lina Buonaguro, Franco M. Tagliamonte, Maria Buonaguro, Luigi J Transl Med Research BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. BioMed Central 2020-01-23 /pmc/articles/PMC6977281/ /pubmed/31973714 http://dx.doi.org/10.1186/s12967-020-02218-x Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Mauriello, Angela
Manolio, Carmen
Cavalluzzo, Beatrice
Avallone, Antonio
Borrelli, Marco
Morabito, Alessandro
Iovine, Emanuele
Chambery, Angela
Russo, Rosita
Tornesello, Maria Lina
Buonaguro, Franco M.
Tagliamonte, Maria
Buonaguro, Luigi
Immunological effects of adjuvants in subsets of antigen presenting cells of cancer patients undergoing chemotherapy
title Immunological effects of adjuvants in subsets of antigen presenting cells of cancer patients undergoing chemotherapy
title_full Immunological effects of adjuvants in subsets of antigen presenting cells of cancer patients undergoing chemotherapy
title_fullStr Immunological effects of adjuvants in subsets of antigen presenting cells of cancer patients undergoing chemotherapy
title_full_unstemmed Immunological effects of adjuvants in subsets of antigen presenting cells of cancer patients undergoing chemotherapy
title_short Immunological effects of adjuvants in subsets of antigen presenting cells of cancer patients undergoing chemotherapy
title_sort immunological effects of adjuvants in subsets of antigen presenting cells of cancer patients undergoing chemotherapy
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977281/
https://www.ncbi.nlm.nih.gov/pubmed/31973714
http://dx.doi.org/10.1186/s12967-020-02218-x
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