3.4.2 Tumor vaccines
Tumor
vaccines, as a form of active immunotherapy, work by providing
tumor-associated antigens and activation signals to stimulate endogenous
tumor-specific T
cells[75]. If
a vaccine can turn ovarian cancer into an immunogenic hot tumor, that is
generating a lot of tumor-specific immune cells, then checkpoint
inhibitors may produce a better response rate in combination
therapy[76]. There is a challenge for cancer vaccines, to identify
the appropriate immune adjuvant that has an ability of non-antigenic
molecules[77] to induce robust immune responses
for the efficacy of vaccines for cancer[78].
Statins should be viewed as a rational vaccine adjuvant.
Xia Y et al. report that lipophilic
statin inhibits the geranylgeranylation of small GTPases, such as Rab5
in antigen-presenting cells (APC), inducing both
Th1 and cytolytic T cell responses,
which of effect are scarce in clinical adjuvants. It also can delay
endosomal antigen entry into degradative lysosomes, that is manipulation
of endocytic maturation without overt inflammatory signals, thus
enhancing antigen presentation[11]. Furthermore,
statins have been established to make myeloid cells sensitive to
external stimuli like lipopolysaccharide (LPS) and to produce cytokines,
and it with IL-2 co-stimulation also activate human NK
cells[78]. A
study in clinic is reported that simvastatin treatment induces
autoantibodies against oxLDL increasing, with an expansion of CD8+ T
cells found[79]. This means that statins may be
used as an adjuvant in tumor vaccines to melt the “coldness” of
ovarian cancer by increasing infiltration by CD8+ T cells, providing a
new view of combination therapy.
Outlook
At present, a mass of clinical
studies and experiments have confirmed the anti-cancer effect of statins
in OC. According to the results of many mechanism studies, it can be
inferred that statins still have great potential in the field of
anti-OC, but due to the limitations of indications of statins usage and
routine treatment regimen in clinic for clinical trial design,
prospective studies are still few. In this review, we found that there
are relatively many studies on the combination of statins with
paclitaxel and platinum drugs, while studies on the combination of
statins with such promising drugs
like bevacizumab, PARP is,
anti-PD/PD-1 and tumor vaccines in
the treatment of ovarian cancer are scarce. In Figures 1, we summarize
the systematic connection of mechanisms about statins associating with
treatment of EOC. Meanwhile, it is also critical to study how to
increase the concentration of statins in the ovaries, rather than the
plasma concentration, for practical application and efficacy. With
researches deepened on statins in the fields of immunotherapy and other
fields, statins have shown a surprising side, which suggests the
necessity of conducting experimental studies on the combination of
statins with the medicines above to provide evidence and confidence for
clinical trials, so as to look forward to entering the clinical trial
stage as soon as possible.
Conflicts of interest
This work was supported by the Shaanxi Provincial Health
Commission[S2020-YF-YBSF-0315];Xi ’an Health Commission
[2023yb03]