A gene expression signature has been discovered that may lead to new immune therapies for patients with lung cancer. NF-KB, a protein complex known to promote tumor growth, may also have the ability to boost the immune system to eliminate cancerous cells before they harm and to promote antitumor responses.
The protein complex NF-KB controls gene expression and plays a role in regulating the body’s immune response to infection. Incorrect regulation of NF-KB has been linked to cancer, inflammatory diseases, autoimmune diseases, septic shock, viral infection, and improper immune development.
Lead author Amer Beg, PhD, of Moffitt Cancer Center in Tampa, Florida, led a team that analyzed the role of NF-KB in lung cancer cells that were used to develop the NF-KB gene signature. Key studies in mice found that NF-KB can mediate immune rejection of tumors, and then these studies were extended to human tumor specimens. This research was published in the Journal of Clinical Investigation (2013;123(6):2509-2522).
Activity of NF-KB was found to be strongly associated with immune system T-cell infiltration in lung cancer. The NF-KB signature was found to have multiple genes that can enhance T-cell responses. So, NF-KB can help facilitate an immune response. The finding that the presence of high levels of NF-KB in lung cancer tumors can act as a suppressor provides new insight into how tumor pathways regulate the antitumor response.
“T-cell presence in tumors can be associated with immune surveillance and improved patient survival,” explained Beg. “The focus of immune therapy, boosting T-cell–induced responses against solid tumors, has shown considerable promise. However, tolerance-inducing mechanisms and the presence of suppressive cell types in the tumor microenvironment can dampen the response to immunotherapy. Our findings provide new insights into beneficial pathways that also operate in tumors and can regulate antitumor responses.”