期刊
CELL STEM CELL
卷 27, 期 2, 页码 238-+出版社
CELL PRESS
DOI: 10.1016/j.stem.2020.06.022
关键词
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资金
- National Institute of Dental and Craniofacial Research [R01 DE15964]
- National Cancer Institute, National Institute of Health, United States [R01CA236878]
PD1 blockade-based combination therapy has been approved as a first-line treatment for head and neck squamous cell carcinoma (HNSCC). However, the response rate remains relatively low, and patients with HNSCC eventually relapse. Here, we show that the combination treatment of anti-PD1 and cisplatin enriched BMI1(+) CSCs in HNSCC while inhibiting HNSCC growth. In contrast, the pharmacological and genetic inhibition of BMI1 eliminated BMI1(+) CSCs and enabled PD1 blockade therapy, resulting in the inhibition of metastatic HNSCC and prevention of HNSCC relapses. BMI1 inhibition strongly induced tumor cell-intrinsic immune responses by recruiting and activating CD8(+) T cells in addition to eliminating BMI1(+) CSCs. Mechanistically, BMI1 inhibition induced CD8(+) T cell-recruiting chemokines by stimulating IRF3-mediated transcription and erasing repressive H2A ubiquitination. Our results suggest that targeting BMI1 may enable immune checkpoint blockade to inhibit metastatic tumor growth and prevent tumor relapse by activating cell-intrinsic immunity, in addition to purging CSCs.
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