The team, from the Walter and Eliza Hall Institute in Australia, also found natural killer cells were critical to the body's rejection of donor bone marrow transplants and in the runaway immune response during toxic shock syndrome.
The team showed that a protein called MCL-1 was crucial for survival of natural killer cells.
The discovery will help to determine how natural killer cells can be manipulated to fight cancers and other disorders.
Researchers said MCL-1 could be a target for boosting or depleting natural killer cell populations to treat disease.
Natural killer cells are immune predators, scouring the body in search of foreign invaders such as viruses, and sensing changes in our own cells that are associated with cancer.
Dr Nick Huntington said the team showed natural killer cells were needed to fight off invading tumour cells that had spread past the original cancer site.
"We discovered MCL-1 is absolutely essential for keeping natural killer cells alive," Huntington said.
"Without natural killer cells, the body was unable to destroy melanoma metastases that had spread throughout the body, and the cancers overwhelmed the lungs," said Huntington.
"Knowing how important natural killer cells are for detecting and destroying cancer cells as they spread suggests they would be a good target for boosting immune defences to treat cancer," said Huntington.
Huntington said the team showed natural killer cells also played a role in death from toxic shock (sepsis), and in rejecting bone marrow transplants.
The research was published in the journal Nature Communications.
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