UC San Diego

The pathology of malignancy and viral infection force cells into the "stressed state," characterized by altered metabolism and imbalanced reactive oxidative species (ROS) ¹⁻³. This generalized state of cellular stress engenders a protective surveillance response by the host immune system⁴⁻¹¹. Under homeostatic conditions, the immune surveillance of stressed cells leads to their destruction; and, thus, many stressed cells experience tremendous selective pressure to develop immune-evasive programs⁵⁻⁸, ¹². Targeting these immune evasive programs in stressed cells as well as identifying the signaling pathways and molecules that influence surveillance have been a top priority¹³⁻¹⁵. We hypothesize that stressed cell-expressed factors can influence the nature and activity of immune cells, thereby determining whether tumors and viral infections progress. To address this central hypothesis, we have endeavored to: First, define how the immune system influences tumor development and progression; Second, explore which signals can recruit immune cells into tumors; and, Third, to determine how cellular stress inherent to malignancy or viral infection induce immune- cell recruiting signals to initiate immunosurveillance