{Reference Type}: Journal Article
{Title}: Hainanenin-1, an oncolytic peptide, triggers immunogenic cell death via STING activation in triple-negative breast cancer.
{Author}: Li X;Su N;Yu H;Li X;Sun SL;
{Journal}: Cell Commun Signal
{Volume}: 22
{Issue}: 1
{Year}: 2024 Jul 5
{Factor}: 7.525
{DOI}: 10.1186/s12964-024-01731-6
{Abstract}: <B>BACKGROUND: </B>In triple-negative breast cancer (TNBC) therapy, insufficient tumor infiltration by lymphocytes significantly hinders the efficacy of immune checkpoint inhibitors. We have previously demonstrated that Hainanenin-1 (HN-1), a host defense peptide (HDP) identified from Hainan frog skin, induces breast cancer apoptosis and boots anti-tumor immunity via unknown mechanism.<BR><B>METHODS: </B>We used in vitro experiments to observe immunogenic cell death (ICD) indicators in HN-1-treated TNBC cell lines, a mouse tumor model to verify HN-1 promotion of mice anti-tumor immune response, and an in vitro drug sensitivity test of patient-derived breast cancer cells to verify the inhibitory effect of HN-1.<BR><B>RESULTS: </B>HN-1 induced ICD in TNBC in a process during which damage-associated molecular patterns (DAMPs) were released that could further increase the anti-tumor immune response. The secretion level of interleukin 2 (IL-2), IL-12, and interferon γ in the co-culture supernatant was increased, and dendritic cells (DCs) were activated via a co-culture with HN-1-pretreated TNBC cells. As a result, HN-1 increased the infiltration of anti-tumor immune cells (DCs and T lymphocytes) in the mouse model bearing both 4T1 and EMT6 tumors. Meanwhile, regulatory T cells and myeloid-derived suppressor cells were suppressed. In addition, HN-1 induced DNA damage, and double-strand DNA release in the cytosol was significantly enhanced, indicating that HN-1 might stimulate ICD via activation of STING pathway. The knockdown of STING inhibited HN-1-induced ICD. Of note, HN-1 exhibited inhibitory effects on patient-derived breast cancer cells under three-dimensional culture conditions.<BR><B>CONCLUSIONS: </B>Collectively, our study demonstrated that HN-1 could be utilized as a potential compound that might augment immunotherapy effects in patients with TNBC.