In:
The Journal of Immunology, The American Association of Immunologists, Vol. 202, No. 1_Supplement ( 2019-05-01), p. 59.10-59.10
Abstract:
Heat shock proteins (HSPs) induce potent immune responses against their chaperoned antigens and thus have potential as cancer immunotherapy. APCs, T cells, and NK cells are all required in HSP-mediated immune responses. NK cells are activated indirectly via APCs, but the mechanism of this activation is poorly understood. Interestingly, MΦ are capable of inducing IFNγ production by NK cells, however, DC are not. This is observed in response to multiple HSPs including gp96, calreticulin and HSP90. Thus, APC production of potential mediators of NK cell activation were investigated. Gp96 induces CXCL10 production in MΦ but not DC and this chemokine is necessary for NK cell activation. Since CXCL10 is STAT1 induced, STAT1 phosphorylation (STAT1p) was examined. A unique pattern of STAT1p is observed in MΦ where S727 is phosphorylated early, followed by delayed phosphorylation of Y701. In contrast, DC exhibit delayed phosphorylation of S727, and phosphorylation of Y701 is not observed. Upstream, p38 MAPK is phosphorylated to comparable levels in both APCs. However, basal expression of the phosphatase SHP2 is higher in DC. Blocking SHP2 in DC leads to earlier phosphorylation of S727 but no recovery of Y701 phosphorylation or subsequent induction of IFNγ production by NK cells. Thus, additional phosphatases and inhibitors are likely contributing to these signaling events. Collectively, these data demonstrate that targeting both MΦ and DC in vivo is critical for optimal HSP-mediated immune responses.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.202.Supp.59.10
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2019
detail.hit.zdb_id:
1475085-5
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