Highlights of This Issue Free

The combination of cyclophosphamide with immunotherapy holds great promise for the clinical success of this treatment modality in cancer patients. Moschella and colleagues, by transcript profiling and multiparametric flow cytometry of blood cells from cancer patients, showed that the ability of cyclophosphamide to trigger the expansion/activation of several components of the innate and adaptive immune system stems from the sterile inflammatory response to the drug-induced death of blood cells through p53 and type I IFN-related mechanisms. These findings have implications for the design of novel combination strategies integrating immunotherapies into the standard of cancer care.

Interleukin (IL)-10 determines viral-associated tumor progression via tumor immune escape. Sung and colleagues show that IL-10 production from E6-positive lung adenocarcinoma cells via the phosphoinositide 3-kinase (PI3K)/AKT pathway promotes tumor aggressiveness. Mechanistically, CIP2A transcription upregulated by IL-10 via the PI3K/AKT pathway is responsible for IL-10–mediated cell invasion. High IL-10 and CIP2A mRNA levels may independently predict poor prognosis in patients with lung adenocarcinoma. Therefore, a PI3K/AKT inhibitor combined with chemotherapy might be useful to suppress tumor progression and metastasis and increase chemosensitivity in patients with high IL-10 mRNA levels.

Federally funded research is lacking for translational studies on brain metastases of systemic cancers, even though they are ten times more frequent than primary brain tumors in humans. Hickey and colleagues address this unmet medical need. They tested a promising multimodal treatment for breast cancer metastatic to the brain that represents a unique combination of cellular immune and gene therapy approaches. Because both experimental therapies are being investigated individually in clinical trials for primary malignant brain tumors, a unique opportunity is presented for rapid translation, not only for breast cancer but also for other systemic malignancies that metastasize to the brain.

A transferrin-conjugated liposome (PTf-Ls) system that could incorporate both the IP-10 gene and fluorescent dyes in a single vesicle offers many opportunities for the application of nanomedicines. To establish such a system, Zhuo and colleagues conducted a series of in vitro experiments to improve the biophysical and cell transfection properties of the PTf-Ls. A nude mouse/breast cancer cell line xenograft model was used to test the clinical utility of the system. The resulting PTf-Ls displayed efficient properties for targeting tumor imaging, gene delivery, and therapy at the same time in vivo, which may open up new avenues for future imaging-guided gene delivery and therapy.