| First Author | Han J | Year | 2020 |
| Journal | Mol Cancer Res | Volume | 18 |
| Issue | 10 | Pages | 1589-1602 |
| PubMed ID | 32591441 | Mgi Jnum | J:300442 |
| Mgi Id | MGI:6502811 | Doi | 10.1158/1541-7786.MCR-19-1226 |
| Citation | Han J, et al. (2020) Inhibition of Aurora-A Promotes CD8(+) T-Cell Infiltration by Mediating IL10 Production in Cancer Cells. Mol Cancer Res 18(10):1589-1602 |
| abstractText | Intratumoral tumor-specific activated CD8(+) T cells with functions in antitumor immune surveillance predict metastasis and clinical outcome in human colorectal cancer. Intratumoral CD8(+) T cells also affect treatment with immune checkpoint inhibitors. Interestingly, inhibition of Aurora kinase A (Aurora-A) by its selective inhibitor alisertib obviously induced infiltration of CD8(+) T cells. However, the mechanisms by which inhibition of Aurora-A promotes infiltration of intratumoral CD8(+) T cells remain unclear. Our recent results demonstrated that conditional deletion of the AURKA gene or blockade of Aurora-A by alisertib slowed tumor growth in association with an increase in the infiltration of intratumoral CD8(+) T cells as well as the mRNA levels of their IL10 receptor alpha (IL10Ralpha). The antitumor effects of targeting Aurora-A were attenuated in the absence of CD8(+) T cells. In addition, antibody-mediated blockade of IL10Ralpha dramatically decreased the percentage of intratumoral CD8(+) T cells. In further experiments, we found that the levels of IL10 were elevated in the serum of azoxymethane/dextran sodium sulfate-treated AURKA(flox/+);VillinCre(+) mice. Unexpectedly, we found that in addition to Aurora-A's mitotic role, inhibition of Aurora-A elevated IL10 transcription, which in turn increased the IL10Ralpha mRNA levels in CD8(+) T cells. Thus, inhibition of Aurora-A could be a useful treatment strategy for recruiting tumor-specific intratumoral CD8(+) T cells. IMPLICATIONS: Understanding the mechanisms by which inhibition of Aurora-A promotes CD8(+) T-cell infiltration and activation, as mediated by the IL10 pathway could provide a potential strategy for tumor immunotherapy. |
