Abstract
While multiple pathways of dendritic cell (DC) maturation result in transient production of IL-12, fully mature DCs show reduced ability to produce IL-12p70 upon a subsequent interaction with Ag-specific T cells, limiting their in vivo performance as vaccines. Such "DC exhaustion" can be prevented by the presence of IFNγ during the maturation of human DCs (type-1-polarization), resulting in improved induction of tumor-specific Th1 and CTL responses in vitro. Here, we show that type-1 polarization of mouse DCs strongly enhances their ability to induce CTL responses against a model tumor antigen, OVA, in vivo, promoting the induction of protective immunity against OVA-expressing EG7 lymphoma. Interestingly, in contrast to the human system, the induction of mouse DC1s requires the participation of IL-4, a nominal Th2-inducing cytokine. The current data help to explain the previously reported Th1-driving and anti-tumor activities of IL-4, and demonstrate that type-1 polarization increases in vivo activity of DC-based vaccines.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1329-1336 |
| Number of pages | 8 |
| Journal | Cancer Immunology, Immunotherapy |
| Volume | 58 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 2009 |
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Keywords
- Dendritic cells
- IL-12
- IL-4
- Lymphoma
- Mouse
- Vaccines
ASJC Scopus subject areas
- Cancer Research
- Immunology
- Immunology and Allergy
- Oncology
Cite this
Type-1 polarized dendritic cells primed for high IL-12 production show enhanced activity as cancer vaccines. / Giermasz, Adam; Urban, Julie A.; Nakamura, Yutaro; Watchmaker, Payal; Cumberland, Rachel L.; Gooding, William; Kalinski, Pawel.
In: Cancer Immunology, Immunotherapy, Vol. 58, No. 8, 08.2009, p. 1329-1336.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Type-1 polarized dendritic cells primed for high IL-12 production show enhanced activity as cancer vaccines
AU - Giermasz, Adam
AU - Urban, Julie A.
AU - Nakamura, Yutaro
AU - Watchmaker, Payal
AU - Cumberland, Rachel L.
AU - Gooding, William
AU - Kalinski, Pawel
PY - 2009/8
Y1 - 2009/8
N2 - While multiple pathways of dendritic cell (DC) maturation result in transient production of IL-12, fully mature DCs show reduced ability to produce IL-12p70 upon a subsequent interaction with Ag-specific T cells, limiting their in vivo performance as vaccines. Such "DC exhaustion" can be prevented by the presence of IFNγ during the maturation of human DCs (type-1-polarization), resulting in improved induction of tumor-specific Th1 and CTL responses in vitro. Here, we show that type-1 polarization of mouse DCs strongly enhances their ability to induce CTL responses against a model tumor antigen, OVA, in vivo, promoting the induction of protective immunity against OVA-expressing EG7 lymphoma. Interestingly, in contrast to the human system, the induction of mouse DC1s requires the participation of IL-4, a nominal Th2-inducing cytokine. The current data help to explain the previously reported Th1-driving and anti-tumor activities of IL-4, and demonstrate that type-1 polarization increases in vivo activity of DC-based vaccines.
AB - While multiple pathways of dendritic cell (DC) maturation result in transient production of IL-12, fully mature DCs show reduced ability to produce IL-12p70 upon a subsequent interaction with Ag-specific T cells, limiting their in vivo performance as vaccines. Such "DC exhaustion" can be prevented by the presence of IFNγ during the maturation of human DCs (type-1-polarization), resulting in improved induction of tumor-specific Th1 and CTL responses in vitro. Here, we show that type-1 polarization of mouse DCs strongly enhances their ability to induce CTL responses against a model tumor antigen, OVA, in vivo, promoting the induction of protective immunity against OVA-expressing EG7 lymphoma. Interestingly, in contrast to the human system, the induction of mouse DC1s requires the participation of IL-4, a nominal Th2-inducing cytokine. The current data help to explain the previously reported Th1-driving and anti-tumor activities of IL-4, and demonstrate that type-1 polarization increases in vivo activity of DC-based vaccines.
KW - Dendritic cells
KW - IL-12
KW - IL-4
KW - Lymphoma
KW - Mouse
KW - Vaccines
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UR - http://www.scopus.com/inward/citedby.url?scp=67349254467&partnerID=8YFLogxK
U2 - 10.1007/s00262-008-0648-5
DO - 10.1007/s00262-008-0648-5
M3 - Article
C2 - 19156413
AN - SCOPUS:67349254467
VL - 58
SP - 1329
EP - 1336
JO - Cancer Immunology, Immunotherapy
JF - Cancer Immunology, Immunotherapy
SN - 0340-7004
IS - 8
ER -