Xia Zhao

Trichostatin A-modified vaccine provides superior protection against ovarian cancer formation and development

More attention has been paid to immunotherapy for ovarian cancer and the development of tumor vaccines. We developed a trichostatin A (TSA)-modified tumor vaccine with potent immunomodulating activities that can inhibit the growth of ovarian cancer in rats and stimulate immune cell response in vivo. TSA-treated Nutu-19 cells inactivated by X-ray radiation were used as a tumor vaccine in rat ovarian cancer models. Prophylactic and therapeutic experiments were performed with TSA-modified tumor vaccine in rats. Flow cytometry and ELISpot assays were conducted to assess immune response. Immune cell expression in the spleen and thymus were detected by immunohistochemical staining. GM-CSF, IL-7, IL-17, LIF, LIX, KC, MCP-1, MIP-2, M-CSF, IP-10/CXCL10, MIG/CXCL9, RANTES, IL-4, IFN-γ, and VEGF expressions were detected with Milliplex Map Magnetic Bead Panel immunoassay. TSA vaccination in therapeutic and prophylactic models could effectively stimulate innate immunity and boost the adaptive humoral and cell-mediated immune responses to inhibit the growth and tumorigenesis of ovarian cancer. This vaccine stimulated the thymus into reactivating status and enhanced infiltrating lymphocytes in tumor-bearing rats. The expression of key immunoregulatory factors were upregulated in the vaccine group. The intensities of infiltrating CD4+ and CD8+ T cells and NK cells were significantly increased in the vaccine group compared to the control group (P<0.05). This protection was mainly dependent on the IFN-γ pathway and, to a much lesser extent, by the IL-4 pathway. The tumor cells only irradiated by X-ray as the control group still showed a slight immune effect, indicating that irradiated cells may also cause certain immune antigen exposure, but the efficacy was not as significant as that of the TSA-modified tumor vaccine. Our study revealed the potential application of the TSA-modified tumor vaccine as a novel tumor vaccine against tumor refractoriness and growth. These findings offer a better understanding of the immunomodulatory effects of the vaccine against latent tumorigenesis and progression. This tumor vaccine therapy may increase antigen exposure, synergistically activate the immune system, and ultimately improve remission rates. A vaccine strategy designed to induce effective tumor immune response is being considered for cancer immunotherapy.

Targeted activation of Stat3 in combination with paclitaxel results in increased apoptosis in epithelial ovarian cancer cells and a reduced tumour burden

AbstractObjectivesStat3 is persistently activated in ovarian cancer cells, with a crucial role in tumour onset and progression. In this study, we examined the anti‐tumour effect of a small‐molecule inhibitor napabucasin (BBI608) on epithelial ovarian cancer (EOC) in vitro and in vivo, and investigated the underlying molecular mechanism of this drug in combination with paclitaxel.Materials and MethodsA total of 156 ovarian cancer patient samples were analysed to determine the correlation between pStat3 expression in tumour cells and the prognosis of EOC patients. The anti‐tumour effect of BBI608 and/or paclitaxel on ovarian cancer in vitro was evaluated by CCK‐8, flow cytometry, Western blot and transwell assays. An in vivo intraperitoneal model was performed to confirm the effect of BBI608 on pStat3‐mediated peritoneal metastasis when combined with paclitaxel.ResultsPatients with high expression of pStat3 had poorer overall survival and progression‐free survival than those with low pStat3 expression. The synergy of BBI608 in combination with paclitaxel exerted dramatic growth inhibition and induced apoptosis in EOC cell lines. In vivo, the combination of two drugs significantly decreased intraperitoneal tumour burden and ascites volume, prolonged survival of tumour‐bearing mice compared with each monotherapy; these results were associated with downregulation of phospho‐Stat3 and activation of apoptosis pathway.ConclusionsTargeting the activation of Stat3 may be a potential therapeutic approach for EOC by acting synergistically with paclitaxel.

Research Progress on Tumor‐Associated Macrophages and Inflammation in Cervical Cancer

Cervical cancer is the most common gynecological tumor worldwide. Persistent infection of high‐risk HPV‐induced smouldering inflammation is considered to be an important risk factor for cervical cancer. The tumor microenvironment (TME) plays an important role in the progress of the tumor occurrence, development, and prognosis of cervical cancer. Macrophages are the main contributor to the TME, which is called tumor‐associated macrophages (TAMs). During the inflammatory response, the phenotype and function of TAMs are constantly changing, which are involved in different regulatory networks. The phenotype of TAMs is related to the metabolism and secretory factors release, which facilitate the angiogenesis and lymphatic duct formation during cervical cancer metastasis, thus affecting the prognosis of cervical cancer. This review intends to discuss the recent research progress on the relationship between TAMs and cervical cancer, which is helpful to elucidate the mechanism of TAMs in cervical cancer.