In:
The Journal of Immunology, The American Association of Immunologists, Vol. 208, No. 1_Supplement ( 2022-05-01), p. 121.11-121.11
Abstract:
The signaling pathways involving phosphoinositide-3-kinases (PI3Ks) are highly conserved and tightly regulated to influence the activation, proliferation, and survival of all cell types. Our lab has recently shown protein TrIP (Transmembrane Inhibitor of PI3K, Pik3ip1) has a distinctly high expression on T cells and is capable of downregulating PI3K signaling in these cells, acting as a negative regulator of T cell immune responses. These studies revealed that CD4+ T cells lacking TrIP expression exhibit a more Th1 inflammatory phenotype compared to WT T cells, both in vivo and in vitro. These data have led us to propose that TrIP restricts the inflammatory activity of T cells more generally, including CD8+ T cells, and that targeting/knockout of this regulator may promote anti-tumor immunity. Using a conditional TrIP knockout mouse model developed in our lab, we have performed syngeneic tumor challenges in CD8+ T cell-specific TrIP knockout mice (TrIPfl/flE8icre) which show that TrIP knockout mice are resistant to growth of syngeneic tumors. In addition to this increased resistance, tumors harvested from our knockout mice contain twice as many infiltrating T cells compared to their WT counterparts. Of those, CD8+ T cells appeared to be the main drivers of this increased T cell infiltration as their frequency was double that of the CD4+ population. In addition, these TrIP KO CD8+ T cells have a significantly more inflammatory phenotype detailed through RNAseq analysis. In conclusion, TrIP plays a significant role in the antitumor immune activity of CD8+ T cells. The TrIP KO mice are resistant to tumor challenge and display an increase in TIL T cell infiltrate. These data describes TrIP as an interesting potential target for immunotherapy. Supported by grants from the NIH 5R01GM136148-02 and 5T32CA082084-20
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.208.Supp.121.11
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2022
detail.hit.zdb_id:
1475085-5
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