Early Events of the Reaction Elicited by CSF-470 Melanoma Vaccine Plus Adjuvants: An In Vitro Analysis of Immune Recruitment and Cytokine Release
In a previous work, we showed that CSF-470 vaccine plus bacillus Calmette–Guerin (BCG) and granulocyte macrophage colony-stimulating factor (GM-CSF) as adjuvants resulted in a significant benefit in the distant metastasis-free survival when comparing vaccinated vs. IFN-α2b-treated high-risk cutaneou...
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Frontiers Media S.A.
2017-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01342/full |
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| author | María B. Pampena María M. Barrio Estefanía P. Juliá Paula A. Blanco Erika M. von Euw José Mordoh José Mordoh José Mordoh Estrella Mariel Levy |
| author_facet | María B. Pampena María M. Barrio Estefanía P. Juliá Paula A. Blanco Erika M. von Euw José Mordoh José Mordoh José Mordoh Estrella Mariel Levy |
| author_sort | María B. Pampena |
| collection | DOAJ |
| description | In a previous work, we showed that CSF-470 vaccine plus bacillus Calmette–Guerin (BCG) and granulocyte macrophage colony-stimulating factor (GM-CSF) as adjuvants resulted in a significant benefit in the distant metastasis-free survival when comparing vaccinated vs. IFN-α2b-treated high-risk cutaneous melanoma patients in a Phase II study. Immune monitoring demonstrated an increase in anti-tumor innate and adaptive immunities of vaccinated patients, with a striking increase in IFN-γ secreting lymphocytes specific for melanoma antigens (Ags). In an effort to dissect the first steps of the immune response elicited by CSF-470 vaccine plus adjuvants, we evaluated, in an in vitro model, leukocyte migration, cytokine production, and monocyte phagocytosis of vaccine cells. Our results demonstrate that leukocytes recruitment, mostly from the innate immune system, is an early event after CSF-470 vaccine plus BCG plus GM-CSF interaction with immune cells, possibly explained by the high expression of CCL2/MCP-1 and other chemokines by vaccine cells. Early release of TNF-α and IL-1β pro-inflammatory cytokines and efficient tumor Ags phagocytosis by monocytes take place and would probably create a favorable context for Ag processing and presentation. Although the presence of the vaccine cells hampered cytokines production stimulated by BCG in a mechanism partially mediated by TGF-β and IL-10, still significant levels of TNF-α and IL-1β could be detected. Thus, BCG was required to induce local inflammation in the presence of CSF-470 vaccine cells. |
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| format | Article |
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| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T14:07:23Z |
| publishDate | 2017-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b887533bdc094512ba0137327125700e2022-12-21T22:58:28ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-10-01810.3389/fimmu.2017.01342298512Early Events of the Reaction Elicited by CSF-470 Melanoma Vaccine Plus Adjuvants: An In Vitro Analysis of Immune Recruitment and Cytokine ReleaseMaría B. Pampena0María M. Barrio1Estefanía P. Juliá2Paula A. Blanco3Erika M. von Euw4José Mordoh5José Mordoh6José Mordoh7Estrella Mariel Levy8Centro de Investigaciones Oncológicas-Fundación Cáncer, Buenos Aires, ArgentinaCentro de Investigaciones Oncológicas-Fundación Cáncer, Buenos Aires, ArgentinaCentro de Investigaciones Oncológicas-Fundación Cáncer, Buenos Aires, ArgentinaCentro de Investigaciones Oncológicas-Fundación Cáncer, Buenos Aires, ArgentinaUCLA JCCC-Translational Oncology Research Labs, Los Angeles, CA, United StatesCentro de Investigaciones Oncológicas-Fundación Cáncer, Buenos Aires, ArgentinaInstituto Médico Especializado Alexander Fleming, Buenos Aires, ArgentinaFundación Instituto Leloir, IIBBA-CONICET, Buenos Aires, ArgentinaCentro de Investigaciones Oncológicas-Fundación Cáncer, Buenos Aires, ArgentinaIn a previous work, we showed that CSF-470 vaccine plus bacillus Calmette–Guerin (BCG) and granulocyte macrophage colony-stimulating factor (GM-CSF) as adjuvants resulted in a significant benefit in the distant metastasis-free survival when comparing vaccinated vs. IFN-α2b-treated high-risk cutaneous melanoma patients in a Phase II study. Immune monitoring demonstrated an increase in anti-tumor innate and adaptive immunities of vaccinated patients, with a striking increase in IFN-γ secreting lymphocytes specific for melanoma antigens (Ags). In an effort to dissect the first steps of the immune response elicited by CSF-470 vaccine plus adjuvants, we evaluated, in an in vitro model, leukocyte migration, cytokine production, and monocyte phagocytosis of vaccine cells. Our results demonstrate that leukocytes recruitment, mostly from the innate immune system, is an early event after CSF-470 vaccine plus BCG plus GM-CSF interaction with immune cells, possibly explained by the high expression of CCL2/MCP-1 and other chemokines by vaccine cells. Early release of TNF-α and IL-1β pro-inflammatory cytokines and efficient tumor Ags phagocytosis by monocytes take place and would probably create a favorable context for Ag processing and presentation. Although the presence of the vaccine cells hampered cytokines production stimulated by BCG in a mechanism partially mediated by TGF-β and IL-10, still significant levels of TNF-α and IL-1β could be detected. Thus, BCG was required to induce local inflammation in the presence of CSF-470 vaccine cells.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01342/fullimmunotherapymelanoma vaccineinnate immunityleukocyte recruitmentpro-inflammatory cytokinesbacillus Calmette–Guerin |
| spellingShingle | María B. Pampena María M. Barrio Estefanía P. Juliá Paula A. Blanco Erika M. von Euw José Mordoh José Mordoh José Mordoh Estrella Mariel Levy Early Events of the Reaction Elicited by CSF-470 Melanoma Vaccine Plus Adjuvants: An In Vitro Analysis of Immune Recruitment and Cytokine Release Frontiers in Immunology immunotherapy melanoma vaccine innate immunity leukocyte recruitment pro-inflammatory cytokines bacillus Calmette–Guerin |
| title | Early Events of the Reaction Elicited by CSF-470 Melanoma Vaccine Plus Adjuvants: An In Vitro Analysis of Immune Recruitment and Cytokine Release |
| title_full | Early Events of the Reaction Elicited by CSF-470 Melanoma Vaccine Plus Adjuvants: An In Vitro Analysis of Immune Recruitment and Cytokine Release |
| title_fullStr | Early Events of the Reaction Elicited by CSF-470 Melanoma Vaccine Plus Adjuvants: An In Vitro Analysis of Immune Recruitment and Cytokine Release |
| title_full_unstemmed | Early Events of the Reaction Elicited by CSF-470 Melanoma Vaccine Plus Adjuvants: An In Vitro Analysis of Immune Recruitment and Cytokine Release |
| title_short | Early Events of the Reaction Elicited by CSF-470 Melanoma Vaccine Plus Adjuvants: An In Vitro Analysis of Immune Recruitment and Cytokine Release |
| title_sort | early events of the reaction elicited by csf 470 melanoma vaccine plus adjuvants an in vitro analysis of immune recruitment and cytokine release |
| topic | immunotherapy melanoma vaccine innate immunity leukocyte recruitment pro-inflammatory cytokines bacillus Calmette–Guerin |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01342/full |
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