Researchers at the Francis Crick Institute in London focused on immune checkpoint blockade therapy and a KRAS inhibitor to block a mutated version of KRAS, a gene that helps control cell growth and death. The mutation is present in about one-third of lung cancer cases, according to the authors (Science Advances, July 20, 2022).

Using mice, the research team found lung tumors with high numbers of active immune cells responded well to the treatment. However, the reverse was also true: When the immune system didn't mount a strong response, the combination was ineffective. The findings also explain why in past human trials those who already went through an immune checkpoint blockade have not responded to KRAS inhibitor treatment -- their tumors didn't have enough active immune cells.

In other findings, mutated KRAS weakens signals that help activate the immune system while boosting hormone-like molecules that foster a supportive environment for the tumor. Also, when the mutated gene was inhibited, the pro-tumor effects did not occur in mice models; fewer cells suppressed the immune system and more cytotoxic T cells were produced to kill cancerous cells.

Future research will focus on other types of cancers and ways to stimulate the immune system to eliminate cancer cells that have developed resistance to renin-angiotensin system (RAS) inhibitors.

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