In this section
@article{Patterson:2024:10.1002/eji.202350635,
author = {Patterson, C and Hazime, K and Zelenay, S and Davis, D},
doi = {10.1002/eji.202350635},
journal = {European Journal of Immunology},
title = {Prostaglandin E impacts multiple stages of the natural killer cell antitumor immune response},
url = {http://dx.doi.org/10.1002/eji.202350635},
volume = {54},
year = {2024}
}
TY - JOUR
AB - Tumor immune escape is a major factor contributing to cancer progression and unresponsiveness to cancer therapies. Tumors can produce prostaglandin E2 (PGE2), an inflammatory mediator that directly acts on Natural killer (NK) cells to inhibit antitumor immunity. However, precisely how PGE2 influences NK cell tumor-restraining functions remains unclear. Here, we report that following PGE treatment, human NK cells exhibited altered expression of specific activating receptors and a reduced ability to degranulate and kill cancer targets. Transcriptional analysis uncovered that PGE also differentially modulated the expression of chemokine receptors by NK cells, inhibiting CXCR3 but increasing CXCR4. Consistent with this, PGE-treated NK cells exhibited decreased migration to CXCL10 but increased ability to migrate toward CXCL12. Using live cell imaging, we showed that in the presence of PGE2, NK cells were slower and less likely to kill cancer target cells following conjugation. Imaging the sequential stages of NK cell killing revealed that PGE impaired NK cell polarization, but not the re-organization of synaptic actin or the release of perforin itself. Together, these findings demonstrate that PGE affects multiple but select NK cell functions. Understanding how cancer cells subvert NK cells is necessary to more effectively harness the cancer-inhibitory function of NK cells in treatments.
AU - Patterson,C
AU - Hazime,K
AU - Zelenay,S
AU - Davis,D
DO - 10.1002/eji.202350635
PY - 2024///
SN - 0014-2980
TI - Prostaglandin E impacts multiple stages of the natural killer cell antitumor immune response
T2 - European Journal of Immunology
UR - http://dx.doi.org/10.1002/eji.202350635
UR - http://hdl.handle.net/10044/1/108356
VL - 54
ER -
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