In Cancer Research this week, researchers from the US and China say that the in vivo programming of tumor antigen-specific T lymphocytes from pluripotent stem cells promotes cancer immunosurveillance. In this study, the team shows that highly reactive antigen-specific cytotoxic T-cells can be generated from induced pluripotent stem cells to provide an unlimited source of functional cytotoxic T cells from immunotherapy. "IPS cell-derived T cells can offer the advantages of avoiding possible immune rejection and circumventing ethical and practical issues associated with other stem cell types," the team writes. "Taken together, our findings offer proof of concept for a potentially more efficient approach to generate antigen-specific T lymphocytes for adoptive immunotherapy."
Also in Cancer Research this week, a team from the UK's Institute for Cancer Studies presents findings from a study of PIF1 helicase's apoptosis suppression mechanism in human tumor cells. In vitro studies have implicated PIF1 in maintaining telomeres and processing DNA replication forks. In this study, the team evaluated the function of the PIF1 gene in human cells by using siRNA knockdown strategies to find out how it responds to DNA replication stress. "We found that PIF1 depletion reduced the survival of both p53-deficient and p53-proficient human tumor cells by triggering apoptosis. In contrast, nonmalignant cells were unaffected by PIF1 depletion," the authors write. "Taken together, our findings suggest roles for PIF1 in S-phase entry and progression that are essential to protect human tumor cells from apoptosis."
And finally in Cancer Research this week, researchers in California say that a blockade of VEGF and c-Met amplifies angiogenesis inhibition in pancreatic islet cancer. Angiogenesis inhibitors that block VEGF receptor signaling slows the growth of many types of tumors, but eventually the disease progresses, the authors write. Multiple strategies are being explored to improve the efficacy of these drugs. In this study, the team compares the cellular effects of small-molecule inhibitors XL880 and XL184 with those of a receptor tyrosine kinase inhibitor, XL999, that blocks VEGFR but not c-Met. "Treatment of RIP-Tag2 mice with XL999 resulted in 43 percent reduction in vascularity of spontaneous pancreatic islet tumors over seven days, but treatment with XL880 or XL184 eliminated approximately 80 percent of the tumor vasculature, reduced pericytes and empty basement membrane sleeves, caused widespread intratumoral hypoxia and tumor cell apoptosis, and slowed regrowth of the tumor vasculature after drug withdrawal," the authors write. "Overall, these findings indicate that inhibition of c-Met and functionally related kinases amplifies the effects of VEGFR blockade."