Low-Intensity Focused Ultrasound Produces Immune Response in Pancreatic Cancer.

Pancreatic adenocarcinoma is an aggressive malignancy with limited therapeutic treatments available and a 5-y survival less than 10%. Pancreatic cancers have been found to be immunogenically "cold" with a largely immunosuppressive tumor microenvironment. There is emerging evidence that focused ultrasound can induce changes in the tumor microenvironment and have a constructive impact on the effect of immunotherapy.

B cell-Derived IL35 Drives STAT3-Dependent CD8 T-cell Exclusion in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDA) is an aggressive malignancy characterized by a paucity of tumor-proximal CD8 T cells and resistance to immunotherapeutic interventions. Cancer-associated mechanisms that elicit CD8 T-cell exclusion and resistance to immunotherapy are not well-known. Here, using a Kras- and p53-driven model of PDA, we describe a mechanism of action for the protumorigenic cytokine IL35 through STAT3 activation in CD8 T cells.

Antitumor Responses in the Absence of Toxicity in Solid Tumors by Targeting B7-H3 via Chimeric Antigen Receptor T Cells.

The high expression across multiple tumor types and restricted expression in normal tissues make B7-H3 an attractive target for immunotherapy. We generated chimeric antigen receptor (CAR) T cells targeting B7-H3 (B7-H3.CAR-Ts) and found that B7-H3.

Featured Article: Nuclear export of opioid growth factor receptor is CRM1 dependent.

Opioid growth factor receptor (OGFr) facilitates growth inhibition in the presence of its specific ligand opioid growth factor (OGF), chemically termed [Met(5)]-enkephalin. The function of the OGF-OGFr axis requires the receptor to translocate to the nucleus. However, the mechanism of nuclear export of OGFr is unknown.

Mutations in the opioid growth factor receptor in human cancers alter receptor function.

The opioid growth factor (OGF)-OGF receptor (OGFr) axis is present and tonically active in animal and human cancer cell lines and tumors. The OGF‑OGFr pathway tonically mediates cell replication in cancer, with OGF serving as an autocrine‑produced inhibitory pentapeptide. The inhibitory effect of OGF on cancer cell replication requires the binding of OGF to OGFr and its trafficking into the nucleus, where it upregulates inhibitory kinase expression, thus suppressing the cell cycle.