Novel drug combo activates natural killer cell immunity to destroy cancer cells

Source: Eurek Alert!, June 2022

UNIVERSITY PARK, Pa. — Most skin cancer drugs that activate the immune system work by triggering immune cells, called T cells, to attack tumors, but when T cells are activated for too long, they can wear out and cease to function. A new study led by Penn State College of Medicine scientists finds that another type of immune cell — natural killer cells — can be harnessed to pick up the slack when T cells no longer work and may also reinvigorate T cells to attack melanoma tumors. The team has identified a unique combination drug strategy to activate this natural killer cell-mediated immunity in mice. The individual agents are clinically used but not in combination, and the combination still must be demonstrated to be effective in humans.

“Long-term effective treatments are difficult to achieve in melanoma patients due to a variety of factors, one of which includes T-cell exhaustion. This occurs occurs over time as cancer patients are treated with drugs to enhance T-cell mediated immunity,” said Gavin Robertson, professor of pharmacology, pathology, dermatology and surgery, Penn State College of Medicine. “If T-cell-mediated immunity is no longer working, switching to an approach that activates natural killer cell-mediated immunity could be a major advancement.”

Robertson explained that natural killer cells can be lacking in solid tumors, likely due to limitations of signals attracting them into tumors, activation once in the tumor, and the general immunosuppressive microenvironment that occurs in tumors. He said that therapies that can increase natural killer cell infiltration and/or activation in tumors are urgently needed.