MAR 22, 2021 6:00 AM PDT

Gene Mutation Keeps Tumors "Cold"

WRITTEN BY: Tara Fernandez

Immunologists have identified a mechanism through which an oncogene mutation shields pancreatic tumors from immune cells. Simultaneously inhibiting mutations in the KRAS gene while boosting immune activity could significantly improve patient outcomes.

Cells called cytotoxic T cells are among the most powerful effectors of the body’s immune response to cancer. They also form the backbone of many successful cancer immunotherapies. However, such therapies don’t work for all patients. Some forms of cancers, known as “cold” tumors, create microenvironments that suppress cytotoxic T cell activity, allowing cancer cells to thrive.

Oleksi Petrenko, an immunologist from Stony Brook University, led a team that investigated the relationship between KRAS and the immune system. Petrenko hypothesized that the oncogene KRAS played a profound role in creating this immunosuppressive environment. 

The KRAS gene is often associated with the deadliest form of cancer, and mutations to the gene are thought to underpin several aspects of cancer establishment and progression. In healthy tissues, the KRAS gene holds instructions for a protein that signals cells to grow and divide.

The team investigated how KRAS influenced tumor immunosuppression in an animal model of pancreatic ductal adenocarcinoma. Tumors in genetically-engineered mice with a KRAS gene deletion became susceptible to immune attack. In contrast, when KRAS was intact, tumors showed no signs of immune cell infiltration.

“We believe that this study clearly demonstrates the ability of oncogenic KRAS to corrupt our anti-tumor immune responses,” said study co-author Nancy C. Reich. “It highlights the need to develop therapeutic interventions that not only target KRAS pathways, but that engage immune cell defense.”

 



Sources: Nature Communications, Stony Brook University.

About the Author
  • Tara Fernandez has a PhD in Cell Biology and has spent over a decade uncovering the molecular basis of diseases ranging from skin cancer to obesity and diabetes. She currently works on developing and marketing disruptive new technologies in the biotechnology industry. Her areas of interest include innovation in molecular diagnostics, cell therapies, and immunology. She actively participates in various science communication and public engagement initiatives to promote STEM in the community.
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