Till now, little is known about the effects of chemotherapy on the immunity of cancer patients and the ideal timing ("window" period) for immunotherapy combined with chemotherapy. In this study, we addressed the immunogenicity of apoptotic ovarian cancer cells induced by paclitaxel and carboplatin, the immunologic aspects in ovarian cancer patients under chemotherapy, and the CTL response when CD8(+) T cells were stimulated with tumor antigen in the "window" period. The immunogenicity of apoptotic ovarian cancer cells was detected first. Then, blood samples from each ovarian cancer patient were obtained before (S(0)) and at days 5-7 (S(1)), days 12-14 (S(2)) and days 25-28 (S(3)) after chemotherapy. The proportions of immunocyte subsets and the function of NK cells were studied. We found that apoptotic ovarian cancer cells elicited a powerful CTL response with antitumor activity in vitro. The proportions of CD3(+) T cells, CD4(+) T cells and the ratio of CD4(+) to CD8(+) cells did not change significantly on S(1), S(2) and S(3), compared to S(0), whereas the percentage of Treg cells decreased remarkably on S(2). The proportions of Th1, Tc1, CD45RO memory T, NKT cells and the ratio of Tc1 to Tc2 cells increased significantly on S(2). IFN-gamma secreting CD8(+) T cells also increased remarkably on S(2), especially when CD8(+) T cells were stimulated with autologous tumor antigen. From our point of view, chemotherapy induces temporary immune reconstitution and augments anti-tumor immune response. It is probable that the "window" period of days 12-14 after chemotherapy provides the best opportunity for immunotherapy.

Background The indoleamine 2, 3-dioxygenase (IDO) inhibitor 1-methyl-tryptophan (1-MT) is currently being used in clinical trials in patients with relapsed or refractory solid tumors by inhibiting tumor immune escape. A greater understanding of IDO activity is required to begin to understand the molecular mechanism by which drugs work. This study was conducted to investigate of the clinical significance of 1-methyl-tryptophan (1-MT) in treating carboplatin-resistant (CBP-resistant) ovarian cancer and its mechanism of action. Methods Using a medium dose, intermittent treatment method, a clinically relevant CBP-resistant human ovarian cancer cell line (SKOV3/CBP) was established. SKOV3/CBP cells were treated with normal serum (control) or 1-MT (0.25 ng/mL) for 4 h (SKOV3/CBP + 1-MT). Cell proliferation, invasion and IDO expression in SKOV3, SKOV3/CBP and SKOV3/CBP + 1-MT cells were determined by MTT assays, Matrigel invasion chambers assays and ELISAs, respectively. The half-maximal inhibitory concentration (IC50) and resistance index (RI) were also calculated. The killing ability of the NK cells and CD8+ T cells co-cultured with SKOV3, SKOV3/CBP and SKOV3/CBP + 1-MT cells were determined by LDH activity assays and the INF-γcounting method. Results The SKOV3/CBP cell line displayed an increased IC50 compared to the SKOV3 cell line (P < 0.05) under CBP treatment. Treatment with 1-MT significantly decreased the IC50 and RI of SKOV3/CBP cells. Furthermore, 1-MT treatment not only reduced the invasion ability, but also suppressed IDO expression in the drug-resistant SKOV3/CBP + 1-MT cell line as compared to the SKOV3/CBP cell line. Furthermore, 1-MT enhanced the killing ability of NK cells and the amount of INF-γsecreted from CD8+ T cells which were co-cultured with the SKOV3/CBP cell line. Conclusion Our data suggested that 1-MT inhibits the invasion of CBP-resistant ovarian cancer cells via down-regulation of IDO expression which leads to re-activation of immune cell function. We provide a conceptual foundation for the clinical development of 1-MT as an anti-tumor immunomodulator for chemotherapy resistant ovarian cancer patients.

Background Chondroitin synthase-1 (CHSY1) is an enzyme responsible for the biosynthesis of chondroitin sulfate, and it has been reported to be involved in tumorigenesis and progression in several cancer types. However, little is known about CHSY1 in ovarian cancer (OC). Methods CHSY1 expression was analysed on a tissue microarray (TMA) including tumour and peritumour tissues of OC patients, and the correlations between CHSY1 and clinicopathological features and prognosis. Gene sequencing analysis and qRT‒PCR were used to identify downstream genes and pathways. Cell function assays were used to assess cell proliferation, invasion and metastasis. Results The study revealed that CHSY1 expression was increased in OC vs. peritumour tissues and positively correlated with prognosis. In vitro cell function assays revealed high CHSY1 expression in OC cells, and CHSY1 was able to promote tumour cell proliferation and tumour cell invasion. Gene sequencing analysis and qRT‒PCR confirmed that CHSY1 promotes OC tumorigenesis through the downstream gene TIAM1 and the ERK signalling pathway. Conclusion Our study revealed a novel role of CHSY1 in OC tumorigenesis and offered a possible therapeutic target for OC.

Background: Ovarian cancer is one of the deadliest and most common gynecological malignancies. This study aims to use comprehensive bioinformatics analysis to try to identify the core candidate genes related to the prediction of ovarian cancer for the early diagnosis and prognosis of ovarian cancer. Methods: Obtain expression profiles from Gene Expression Omnibus database, identify differentially expressed genes (DEG) with p<0.05 and (logFC)>1.5, perform functional enrichment, protein-protein interaction (PPI) network construction, functional module analysis, and survival analysis And correlation analysis to obtain the target gene, through immunohistochemical staining, clinicopathological feature analysis to verify the expression and clinical significance of TTK.Results: 1. Identified 135 genes with the same expression. 33 up-regulated DEG were mainly enriched in mitotic spindle assembly checkpoints, chromosome segregation regulation, etc.; 102 down-regulated DEG was mainly enriched in neurotransmitter level regulation, protein serine/threonine Regulation of acid kinase activity, etc. Then the PPI network was constructed to screen 20 hub genes and perform survival analysis and expression correlation analysis. At the same time, the modules that met the requirements were screened and the genes were analyzed by pathway enrichment. It was found that TTK was highly expressed in ovarian cancer and led to a poor prognosis.2. Distant metastasis, lymph node metastasis, clinical staging (stage III-IV), and poor differentiation are independent risk factors for high TTK expression (P<0.05).3. TTK, CA125, HE4 three biological indicators show excellent diagnostic value in joint monitoring of ovarian cancer.Conclusions: TTK plays a vital role in the tumorigenesis, aggressiveness and malignant biological behavior of EOC, and can be used as a potential biomarker and potential therapeutic target for early diagnosis and predictive evaluation of EOC.