Protein Complex Linked to Cancer Growth May Act as Tumor Suppressor
Researchers at Moffitt Cancer Center in Tampa, Florida, and Tianjin Medical University Cancer Institute and Hospital in China have discovered a gene-expression signature that may lead to new immune therapies for patients with lung cancer. Their findings, published in The Journal of Clinical Investigation, suggest that that NF-κB, a protein complex known to promote tumor growth, may also have the ability to boost the immune system to eliminate cancerous cells before they can cause harm, as well as promote antitumor responses.
NF-κB is a protein complex that controls gene expression. The regulation of NF-κB also plays an important role in regulating the body’s immune response to infection. Incorrect regulation of NF-kB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development.
“New insight into how tumor pathways regulate the antitumor immune response may help us to devise new ways for improving immune therapy,” said study lead author Amer Beg, PhD, senior member of Moffitt’s Immunology Program. “Studies are now underway to start a clinical trial to determine whether the novel gene-expression signature described in this work may help initiate new and better immunotherapy treatments.”
Study Details
The researchers analyzed the role of NF-κB in lung cancer cells that were used to develop the NF-κB gene signature. Key studies in mice showed that high NF-κB activity can mediate immune rejection of tumors. The studies were then extended to human lung tumor specimens.
“In this study, we found that NF-κB activity is strongly associated with immune system T-cell infiltration in lung cancer,” explained study coauthor Dung-Tsa Chen, PhD, a member of the Biostatistics Department at Moffitt. “Multiple genes capable of enhancing T-cell responses were found in the NF-κB signature. This means that NF-κB, thought of as a tumor promoter, also helps facilitate an immune response.”
Their finding—that the presence of high levels of NF-κB 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 Dr. 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.”
This work was supported by a National Cancer Institute lung cancer SPORE grant (P50 CA119997), the National Functional Genomics Center, and the James and Esther King Biomedical Research Program.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
