Effect of Modified Vaccinia Ankara-5T4 and Low-Dose Cyclophosphamide on Antitumor Immunity in Metastatic Colorectal Cancer: A Randomized Clinical Trial.

Importance: The success of immunotherapy with checkpoint inhibitors is not replicated in most cases of colorectal cancer; therefore, different strategies are urgently required. The oncofetal antigen 5T4 is expressed in more than 90% of cases of metastatic colorectal cancer (mCRC). Preliminary data using modified vaccinia Ankara-5T4 (MVA-5T4) in mCRC demonstrated that it safely induced serologic and T-cell responses.

Low-Dose Cyclophosphamide Induces Antitumor T-Cell Responses, which Associate with Survival in Metastatic Colorectal Cancer.

Anticancer T-cell responses can control tumors, but immunosuppressive mechanisms prevent their function. The role of regulatory T cells (Tregs) in metastatic colorectal cancer is unclear. We have previously shown depletion of Tregs enhances colorectal cancer-specific effector T-cell responses.

Fibrofatty Band-Associated Small Bowel Obstruction After Marathon Running.

We report a 57-year-old man who developed subacute small bowel obstruction after running a marathon. A fibrofatty band was identified restricting the terminal ileum upon subsequent imaging. Surgical division of the band resulted in complete resolution of the patient's symptoms.

Tracking the kinetics of intrahepatic immune responses by repeated fine needle aspiration of the liver.

Liver disease is an increasing global health burden. The final sequalae of cirrhosis, liver failure and hepatocellular carcinoma are often the result of inflammation driven by intrahepatic lymphocytes. Accurate assessment of organ-specific diseases ideally employs tissue sampling though this is rarely performed.

Escalating regulation of 5T4-specific IFN-γ CD4 T cells distinguishes colorectal cancer patients from healthy controls and provides a target for therapy.

The relationship between the adaptive CD4 T cell response and human cancer is unclear. The oncofetal antigen 5T4 is expressed on many human carcinomas, including colorectal cancer (CRC) cells, but has limited expression on normal tissues. We previously identified anti-5T4 CD4 T cells in a proportion of CRC patients, and we extended this study to examine whether the quality or quantity of the T cell response reflects tumor stage.

The paradox of NKp46+ natural killer cells: drivers of severe hepatitis C virus-induced pathology but in-vivo resistance to interferon α treatment.

Objective: There is evidence that natural killer (NK) cells help control persistent viral infections including hepatitis C virus (HCV). The phenotype and function of blood and intrahepatic NK cells, in steady state and after interferon (IFN) α treatment has not been fully elucidated.

Design: We performed a comparison of NK cells derived from blood and intrahepatic compartments in multiple paired samples from patients with a variety of chronic liver diseases.

Rapid early innate control of hepatitis C virus during IFN-α treatment compromises adaptive CD4+ T-cell immunity.

The ability to control HCV with IFN-α-based treatments provides an opportunity in humans to study how the rate of viral clearance in vivo impinges on the development of antiviral responses. Ex vivo (IFN-γ-producing) and cultured antiviral CD4(+) T cells, serum cytokines, and viral loads were measured repeatedly in a cohort of chronically HCV-infected subjects (n = 33) receiving IFN-α. Rapid control of virus indicated by an increased calculated rate of virus clearance, occurred in those subjects demonstrating absent/minimal T-cell responses (p < 0.