Currently, lack of diagnostics is a fundamental cause of lung cancer mortality, as tumors are often inoperable or metastatic by the time they are detected. Nonetheless, low-dose computed tomography screens may change diagnostic prospects in the future, and recently developed therapies targeting tumors harboring mutations in EGFR or ALK receptors are showing promise.

Equally lethal is metastatic lung cancer, with an approximate 85% mortality within 5 years of diagnosis. In these circumstances, cells from primary tumors in breast, colon, prostate, or other organs invade lung tissue via the bloodstream. LJI scientists are now exploiting immunotherapy approaches to antagonize these malignancies by identifying subclasses of immune cells capable of fending off invaders.

Immunological Invisibility Cloak
Among them is Joel Linden, Ph.D., who recently reported that jamming signals transmitted by membrane proteins called adenosine receptors, which are expressed on T cells and on specialized cell-killing cells called NK cells, made both cell types more effective in halting lung metastasis of melanoma cells. Intriguingly, secretion of adenosine by tumor cells activates those receptors and is one way tumors build an “immunosuppressive shield” around themselves. Linden’s lab is now experimenting with adenosine receptor blockers capable of breaking through that shield to stimulate immune rejection of cancers.

LJI’s Catherine Hedrick, Ph.D., recently discovered that a population of white blood cells called “patrolling monocytes”, protects against lung metastasis. Although, Hedrick and Linden target different cell types, innovations by both groups could encourage clinical tests of drugs designed to switch on a patient’s immune cells by eradicating secondary lung malignancies.