INDIANAPOLIS — New research from Indiana University School of Medicine scientists revealed that a well-known cancer-fighting gene also plays an unexpected role in regulating how certain immune cells can support tumor growth. This insight into pancreatic cancer progression could lead to more effective treatments against one of the deadliest forms of cancer.
The study, recently published in Science Advances, focused on M2-like macrophages, a subtype of immune cells found in the tumor environment that are known to weaken the body’s ability to fight cancer. The researchers examined how a gene called serine/threonine kinase 11 (STK11) influences these cells. They found that when STK11 is missing in macrophages, those cells switch into a tumor-supporting state.
“STK11 was originally identified as a tumor suppressor and extensive studies have examined the gene’s functions and mechanisms in regulating cancer cell growth,” said Kai Yang, PhD, corresponding author of the study, an associate professor of pediatrics and microbiology and immunology at the IU School of Medicine and a researcher with the Indiana University Melvin and Bren Simon Comprehensive Cancer Center. “What surprised us in our screening was seeing its role in coupling M2-like macrophage metabolism and function. Instead of acting directly on tumors, STK11 helps keep macrophages from protecting cancer. When the gene is missing, those cells actually make it easier for cancer to grow.”
In a pancreatic cancer mouse model, the researchers noticed the loss of STK11 in macrophages accelerated tumor progression. The findings reveal a previously unknown role for STK11 in shaping how M2-like macrophages behave inside tumors.
“Our findings suggest that enhancing STK11 activity or blocking the ways that help them grow may counteract their tumor-protecting power and make treatments for pancreatic cancer and other cancers more effective,” Yang said.
The next phase of research will further investigate how STK11 in M2-like macrophages shapes the tumor immune microenvironment as cancer advances.
Additional IU co-authors of the study include Jing Yang, Naresh Singh, Chengxian Xu, Samantha Sharma, Sheng Liu, Joseph Lechner, Martin J. Richer, Yong Zang, Xiumei Huang, Reuben Kapur, Jun Wan and Xinna Zhang.
This research was supported by funding from the National Institutes of Health.
About the Indiana University School of Medicine
The IU School of Medicine is the largest medical school in the U.S. and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability. According to the Blue Ridge Institute for Medical Research, the IU School of Medicine ranks No. 13 in 2024 National Institutes of Health funding among all public medical schools in the country.
Writer: Jackie Maupin, jacmaup@iu.edu
For more news, visit the IU School of Medicine Newsroom: medicine.iu.edu/news
The study, recently published in Science Advances, focused on M2-like macrophages, a subtype of immune cells found in the tumor environment that are known to weaken the body’s ability to fight cancer. The researchers examined how a gene called serine/threonine kinase 11 (STK11) influences these cells. They found that when STK11 is missing in macrophages, those cells switch into a tumor-supporting state.
“STK11 was originally identified as a tumor suppressor and extensive studies have examined the gene’s functions and mechanisms in regulating cancer cell growth,” said Kai Yang, PhD, corresponding author of the study, an associate professor of pediatrics and microbiology and immunology at the IU School of Medicine and a researcher with the Indiana University Melvin and Bren Simon Comprehensive Cancer Center. “What surprised us in our screening was seeing its role in coupling M2-like macrophage metabolism and function. Instead of acting directly on tumors, STK11 helps keep macrophages from protecting cancer. When the gene is missing, those cells actually make it easier for cancer to grow.”
In a pancreatic cancer mouse model, the researchers noticed the loss of STK11 in macrophages accelerated tumor progression. The findings reveal a previously unknown role for STK11 in shaping how M2-like macrophages behave inside tumors.
“Our findings suggest that enhancing STK11 activity or blocking the ways that help them grow may counteract their tumor-protecting power and make treatments for pancreatic cancer and other cancers more effective,” Yang said.
The next phase of research will further investigate how STK11 in M2-like macrophages shapes the tumor immune microenvironment as cancer advances.
Additional IU co-authors of the study include Jing Yang, Naresh Singh, Chengxian Xu, Samantha Sharma, Sheng Liu, Joseph Lechner, Martin J. Richer, Yong Zang, Xiumei Huang, Reuben Kapur, Jun Wan and Xinna Zhang.
This research was supported by funding from the National Institutes of Health.
About the Indiana University School of Medicine
The IU School of Medicine is the largest medical school in the U.S. and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability. According to the Blue Ridge Institute for Medical Research, the IU School of Medicine ranks No. 13 in 2024 National Institutes of Health funding among all public medical schools in the country.
Writer: Jackie Maupin, jacmaup@iu.edu
For more news, visit the IU School of Medicine Newsroom: medicine.iu.edu/news