Dendritic Cell-Based Vaccines Recruit Neutrophils to the Local Draining Lymph Nodes to Prime Natural Killer Cell Responses
Dendritic cell (DC)-based cancer vaccines are a form of immunotherapy that activates the innate and adaptive immune systems to combat cancers. Neutrophils contribute to cancer biology and have the potential to be exploited by immunotherapeutic platforms to enhance anti-tumor immune responses. We pre...
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MDPI AG
2022-12-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/1/121 |
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| author | Lily Chan Yeganeh Mehrani Geoffrey A. Wood Byram W. Bridle Khalil Karimi |
| author_facet | Lily Chan Yeganeh Mehrani Geoffrey A. Wood Byram W. Bridle Khalil Karimi |
| author_sort | Lily Chan |
| collection | DOAJ |
| description | Dendritic cell (DC)-based cancer vaccines are a form of immunotherapy that activates the innate and adaptive immune systems to combat cancers. Neutrophils contribute to cancer biology and have the potential to be exploited by immunotherapeutic platforms to enhance anti-tumor immune responses. We previously showed that DC vaccines elicit the expansion of mouse interferon (IFN)γ-producing mature natural killer (NK) cells to elevate anti-tumor responses. Here, we demonstrate the rapid recruitment of neutrophils to the draining lymph nodes of DC-vaccinated mice. This was accompanied by an increase in the total number of NK cells producing IFN<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>γ</mi></semantics></math></inline-formula> and expressing CD107a, a marker of degranulation that demonstrates NK cell functional activity. Furthermore, the depletion of neutrophils in DC-immunized mice resulted in decreased numbers of NK cells in draining lymph nodes compared to the controls. Interestingly, the increased number of IFNγ- and CD107a-expressing NK cells in DC-immunized mice was not detected in mice depleted of neutrophils. Further investigations showed that DC vaccines induced IFN<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mi>γ</mi><mo>−</mo></mrow></semantics></math></inline-formula> and TNF<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>α</mi></semantics></math></inline-formula>-producing CD8+ T cells that also expressed CD107a, but depletion of neutrophils did not have any impact on the CD8+ T cell population. Our findings suggest that neutrophil-mediated anti-tumor immunity induced by a DC vaccine platform could be targeted to provide innovative strategies to enhance its clinical efficacy. |
| first_indexed | 2024-03-11T10:05:15Z |
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| last_indexed | 2024-03-11T10:05:15Z |
| publishDate | 2022-12-01 |
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| series | Cells |
| spelling | doaj.art-c1b504cff1374a3496baf4d391a1e6622023-11-16T15:06:29ZengMDPI AGCells2073-44092022-12-0112112110.3390/cells12010121Dendritic Cell-Based Vaccines Recruit Neutrophils to the Local Draining Lymph Nodes to Prime Natural Killer Cell ResponsesLily Chan0Yeganeh Mehrani1Geoffrey A. Wood2Byram W. Bridle3Khalil Karimi4Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, CanadaDendritic cell (DC)-based cancer vaccines are a form of immunotherapy that activates the innate and adaptive immune systems to combat cancers. Neutrophils contribute to cancer biology and have the potential to be exploited by immunotherapeutic platforms to enhance anti-tumor immune responses. We previously showed that DC vaccines elicit the expansion of mouse interferon (IFN)γ-producing mature natural killer (NK) cells to elevate anti-tumor responses. Here, we demonstrate the rapid recruitment of neutrophils to the draining lymph nodes of DC-vaccinated mice. This was accompanied by an increase in the total number of NK cells producing IFN<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>γ</mi></semantics></math></inline-formula> and expressing CD107a, a marker of degranulation that demonstrates NK cell functional activity. Furthermore, the depletion of neutrophils in DC-immunized mice resulted in decreased numbers of NK cells in draining lymph nodes compared to the controls. Interestingly, the increased number of IFNγ- and CD107a-expressing NK cells in DC-immunized mice was not detected in mice depleted of neutrophils. Further investigations showed that DC vaccines induced IFN<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mi>γ</mi><mo>−</mo></mrow></semantics></math></inline-formula> and TNF<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>α</mi></semantics></math></inline-formula>-producing CD8+ T cells that also expressed CD107a, but depletion of neutrophils did not have any impact on the CD8+ T cell population. Our findings suggest that neutrophil-mediated anti-tumor immunity induced by a DC vaccine platform could be targeted to provide innovative strategies to enhance its clinical efficacy.https://www.mdpi.com/2073-4409/12/1/121neutrophilsdendritic cell vaccinecrosstalkimmunobiologynatural killer cells |
| spellingShingle | Lily Chan Yeganeh Mehrani Geoffrey A. Wood Byram W. Bridle Khalil Karimi Dendritic Cell-Based Vaccines Recruit Neutrophils to the Local Draining Lymph Nodes to Prime Natural Killer Cell Responses Cells neutrophils dendritic cell vaccine crosstalk immunobiology natural killer cells |
| title | Dendritic Cell-Based Vaccines Recruit Neutrophils to the Local Draining Lymph Nodes to Prime Natural Killer Cell Responses |
| title_full | Dendritic Cell-Based Vaccines Recruit Neutrophils to the Local Draining Lymph Nodes to Prime Natural Killer Cell Responses |
| title_fullStr | Dendritic Cell-Based Vaccines Recruit Neutrophils to the Local Draining Lymph Nodes to Prime Natural Killer Cell Responses |
| title_full_unstemmed | Dendritic Cell-Based Vaccines Recruit Neutrophils to the Local Draining Lymph Nodes to Prime Natural Killer Cell Responses |
| title_short | Dendritic Cell-Based Vaccines Recruit Neutrophils to the Local Draining Lymph Nodes to Prime Natural Killer Cell Responses |
| title_sort | dendritic cell based vaccines recruit neutrophils to the local draining lymph nodes to prime natural killer cell responses |
| topic | neutrophils dendritic cell vaccine crosstalk immunobiology natural killer cells |
| url | https://www.mdpi.com/2073-4409/12/1/121 |
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