Autologous CTL response against cancer stem-like cells/cancer-initiating cells of bone malignant fibrous histiocytoma
Cancer stem cells (CSCs) are potentially ideal therapeutic targets for eliminating tumor cells due to their ability to self-renew, differentiate, and promote tumorigenesis. However, CSCs have proven resistant to standard therapies such as radiation and chemotherapy. Cytotoxic T lymphocyte-based immunotherapy with peptide vaccination has shown promise for treating some chemotherapy-resistant cancers. In order to investigate the efficacy of CTL-based immunotherapy for CSCs, Kano and colleagues analyzed autologous CTL responses against side population (SP) cells in the bone malignant fibrous histiocytoma cell line MFH2003. Kano and colleagues have previously determined CSC characteristics in MFH2003 SP cells. The researchers now report that MFH2003 SP cells expressed more HLA class I on the cell surface than main population cells and that SP cells were recognized by autologous tumor-infiltrating lymphocytes. Furthermore, an autologous CTL clone, induced by mixed lymphocyte tumor cell culture with SP cells as antigens, showed specific cytotoxicity against SP cells. These results suggest that CTL-based immunotherapy may be a promising therapy against bone sarcoma CSCs.
Metronomic doxifluridine chemotherapy combined with the anti-angiogenic agent TNP-470 inhibits the growth of human uterine carcinosarcoma xenografts
Uterine sarcoma, one of the most aggressive gynecological cancers, is resistant to radiotherapy and conventional chemotherapy. Studies suggest that uterine sarcoma’s invasiveness and metastatic potential could be associated with its highly angiogenic nature. Metronomic chemotherapy, which involves frequent, lower doses of cytotoxic agents, is a new treatment approach. Its mechanism may involve angiogenesis suppression. Studies show that metronomic chemotherapy combined with anti-angiogenic agents results in synergistic antitumor effects. Naganuma and colleagues investigated the effects of metronomic chemotherapy with doxifluridine, a widely used anticancer agent, in combination with TNP-470, a broad-spectrum angiogenesis inhibitor. Metronomic doxifluridine combined with TNP-470 significantly inhibited the growth and angiogenesis of uterine carcinosarcoma xenografts, compared with either treatment alone. In addition, the combined treatment of metronomic doxifluridine and TNP-470 caused fewer toxicities than the maximum tolerated dose of doxifluridine combined with TNP-470. The authors call for human clinical studies to further examine the potential of this treatment for uterine carcinosarcoma.
Tumor stroma reaction-related gene signature predicts clinical outcome in human hepatocellular carcinoma
Tumor stromal cells play a critical role in tumorigenesis and are a potential source of new tumor biomarkers. However, the role of stromal gene expression in hepatocellular carcinoma (HCC) remains largely unknown. As the fifth most common cancer worldwide and the third leading cause of cancer death, HCC requires further research towards more effective treatments. To better elucidate the mechanisms of HCC, Gao and colleagues analyzed the expression of 28 stroma-related genes that have been implicated in HCC progression. Hierarchical clustering based on the expression of the 28 genes successfully classified HCC patients into prognostic subgroups. The researchers also evaluated a group of marker genes for intratumoral stromal reactions and the immune response. A five-gene classifier was found to significantly predict HCC recurrence. The authors suggest that this novel predictor might contain targets for new therapeutic interventions.