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Anti–CTLA‐4 synergizes with dendritic cell–targeted vaccine to promote IL‐3–dependent CD4+ effector T cell infiltration into murine pancreatic tumors.
- Source :
- Annals of the New York Academy of Sciences; Jun2019, Vol. 1445 Issue 1, p62-73, 12p, 4 Graphs
- Publication Year :
- 2019
-
Abstract
- One successful class of cancer immunotherapies, immune checkpoint inhibitory antibodies, disrupts key pathways that regulate immune checkpoints, such as cytotoxic T lymphocyte–associated antigen‐4 (CTLA‐4). These agents unleash the potency of antigen‐experienced T cells that have already been induced as a consequence of the existing tumor. But only 20% of cancers naturally induce T cells. For most cancers, vaccines are require to induce and mobilize T effector cells (Teffs) to traffick into tumors. We evaluated the effects of anti–CTLA‐4 given in combination with an antigen‐specific dendritic cell vaccine on intratumoral Teffs in a murine pancreatic cancer model. The dendritic cell–targeted tumor antigen plus anti–CTLA‐4 significantly increased the number of vaccine‐induced CD4+ Teffs within the tumor. This increase was accompanied by a reduction in the size of the peripheral CD4+ Teff pool. We also found that IL‐3 production by activated CD4+ T cells was significantly increased with this combination. Importantly, the CD4+ Teff response was attenuated in Il3−/− mice, suggesting mediation of the effect by IL‐3. Finally, the induced T cell infiltration was associated with activation of the tumor endothelium by T cell–derived IL‐3. Our findings collectively provide a new insight into the mechanism driving Teff infiltration and vascular activation in a murine pancreatic cancer model, specifically identifying a new role for IL‐3 in the anticancer immune response. [ABSTRACT FROM AUTHOR]
- Subjects :
- T cells
PANCREATIC tumors
TUMOR antigens
CYTOTOXIC T cells
VACCINES
PANCREATIC cancer
Subjects
Details
- Language :
- English
- ISSN :
- 00778923
- Volume :
- 1445
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Annals of the New York Academy of Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 137029667
- Full Text :
- https://doi.org/10.1111/nyas.14049