BMI1 Inhibition Eliminates Residual Cancer Stem Cells after PD1 Blockade and Activates Antitumor Immunity to Prevent Metastasis and Relapse.

ABSTRACT: 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 C

SUBMITTER: Jia L 

PROVIDER: S-EPMC7416748 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature