Compounds having the following Formula I and/or Formula II and methods of their use and preparation are disclosed: ##STR00001##

The invention provides methods of modulating follicular regulatory T (TFR) cell-mediated immune responses and the use of those methods in the treatment of diseases or conditions such as viral, bacterial, pathogenic, or fungal infections or cancer. Such methods provide for boosting of antibody production through the use of IL-21 to overcome TFR cell suppression of antibody production.

The invention provides methods of modulating follicular regulatory T (TFR) cell-mediated immune responses and the use of those methods in the treatment of diseases or conditions such as viral, bacterial, pathogenic, or fungal infections or cancer. Such methods provide for boosting of antibody production through the use of IL-21 to overcome TFR cell suppression of antibody production.

Genetically modified cells, tissues, and organs for treating or preventing diseases are disclosed. Also disclosed are methods of making the genetically modified cells and non-human animals.

Genetically modified cells, tissues, and organs for treating or preventing diseases are disclosed. Also disclosed are methods of making the genetically modified cells and non-human animals.

The present invention provides use of an agent that inhibits EP4 activity and an immuno-oncology agent, or a composition thereof, for treatment of a cancer.

The present invention provides use of an agent that inhibits EP4 activity and an immuno-oncology agent, or a composition thereof, for treatment of a cancer.

Adiponectin-expressing thymocytes and compositions comprising the thymocytes are provided. Methods are provided for using the adiponectin-expressing thymocytes for metabolic regulation and treatment of hyperproliferative diseases.

Adiponectin-expressing thymocytes and compositions comprising the thymocytes are provided. Methods are provided for using the adiponectin-expressing thymocytes for metabolic regulation and treatment of hyperproliferative diseases.

The invention described herein features methods and compositions for modifying thymic function and/or activity in a subject (e.g., a human, e.g., a human patient in need thereof; or a non-human animal, e.g., a companion animal or an agricultural animal).