美国加州大学洛杉矶分析Cun-Yu Wang研究团队发现，BMI1抑制可消除PD1阻断后残留的肿瘤干细胞（CSC），并激活抗肿瘤免疫功能来防止转移和复发。该项研究成果于2020年7月21日在线发表在《细胞—干细胞》杂志上。

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

Author: Lingfei Jia, Wuchang Zhang, Cun-Yu Wang

Issue&Volume: 2020-07-21

Abstract: PD1 blockade-based combination therapy has been approved as a first-line treatmentfor head and neck squamous cell carcinoma (HNSCC). However, the response rate remainsrelatively low, and patients with HNSCC eventually relapse. Here, we show that thecombination treatment of anti-PD1 and cisplatin enriched BMI1+ CSCs in HNSCC while inhibiting HNSCC growth. In contrast, the pharmacological andgenetic inhibition of BMI1 eliminated BMI1+ CSCs and enabled PD1 blockade therapy, resulting in the inhibition of metastaticHNSCC and prevention of HNSCC relapses. BMI1 inhibition strongly induced tumor cell-intrinsicimmune 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 erasingrepressive H2A ubiquitination. Our results suggest that targeting BMI1 may enableimmune checkpoint blockade to inhibit metastatic tumor growth and prevent tumor relapseby activating cell-intrinsic immunity, in addition to purging CSCs.

DOI: 10.1016/j.stem.2020.06.022

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30289-7