3.4 Immunotherapy
3.4.1 Anti-PD1/PD-L1
Programmed death ligand 1 (PD-L1) is the main ligand of programmed death receptor 1 (PD1) on T cells. The combination between the two strongly inhibits T cell receptor (TCR) signaling and CD80/CD28 co-stimulation leads to tumors evading detection tumors evade detection[66]. Many tumors take advantage of this negative immunomodulatory mechanism by upregulating the expression of PD-L1, thus benefiting their survival[67]. OC is usuallly regarded as a “cold tumor”, for the reduced infiltration by immune cells, especially CD8+ T cells[68]. Clinical trial results show the low efficacy of anti-PD1 /PD-L1 monotherapy[69]. Therefore, EOC has been establish to be immunogenic, but no immunotherapy has been approved to date. To improve the anti-PD1 /PD-L1 response rate, multiple treatment strategies are currently being investigated. Notably, it has indicated that statins lead to better clinical outcomes in malignant pleural mesothelioma (MPM) and advanced non-small cell lung cancer (NSCLC) patients treated with nivolumab, a PD1-targeting antibody, suggesting that statins with immune checkpoint inhibitors are promising for combination cancer therapy.[11,70][] Otherwise, phosphorylated and activatedβ-catenin-S552 through AKT can supress statin-mediated PD-L1 in lung cancer and melanoma cells[72]. Statins combinating with anti-PD-1 antibody could strengthen the efficacy of immunotherapy for head and neck squamous cell carcinoma (HNSCC) and the effect of cisplatin to struggle with it by inducing calreticulin exposure and ER stress in a cancer-specific manner and promote HNSCC cell death[73]. And statins are also confirmed to activate tumor-specific CD8+ T cells and antigen-presenting cells to increase their numbers in the tumor tissues[74]. Meanwhile, as the MVAP inhibitors, statins are robust for synergizing with anti-PD-1 antibodies in multiple mouse cancer models[11]. It indicates that statins are likely to have a synergistic effect with anti-PD1/PD-L1, this new combination therapy of ovarian cancer can be validated in basic experiments before further designing reasonable clinical trials.