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.