(Press-News.org) GRAND RAPIDS, Mich. (June 27, 2025) — Van Andel Institute scientists and collaborators have discovered a potential treatment target that may re-energize dysfunctional or “exhausted” immune cells in their fight against cancer.
The target is an immune checkpoint called PTGIR, which regulates the number and cancer-fighting powers of T cells, the soldiers of the immune system. Too much PTGIR puts a brake on T cells and reduces their ability to release cancer-killing molecules.
The findings, published in the journal Nature Immunology, could help improve cancer immunotherapies by paving the way for new immune checkpoint inhibitors or engineered T cell therapies that block PTGIR signaling and re-invigorate T cells.
“Immunotherapies are game changers for cancer treatment, but they don’t work for everyone or for all cancers,” said Michael Dahabieh, Ph.D., the study’s first author and a postdoctoral fellow in the lab of Russell Jones, Ph.D., at VAI. “Blocking PTGIR offers another opportunity to develop more targeted treatments that help the immune system fight disease.”
Immune checkpoints are molecules that pepper the outside of T cells and some cancer cells. In immune cells, checkpoints help the immune system do its job without accidentally attacking healthy cells. In cancer, checkpoints allow malignant cells to evade immune attacks. Medications that block checkpoints, called immune checkpoint inhibitors, have become powerful tools for treating cancer.
Most known immune checkpoints rely on interactions between proteins, which can limit treatment options. The new checkpoint is based on a protein (PTGIR) and a lipid (prostacyclin), which creates new prospects for leveraging the checkpoint to fight cancer. To date, only a few similar protein-lipid interactions have been described in T cells.
Prostacyclin is found in and around tumors and contributes to T cell exhaustion by interacting with PTGIR. The amount and availability of PTGIR is regulated by another protein called NRF2. More NRF2 means more PTGIR — which results in widespread T cell exhaustion.
“The more PTGIR, the more opportunities there are for it to interact with prostacyclin,” Jones said. “This increased activity slams the brakes on T cell activity and makes it more difficult for them to continue fighting cancer cells. Shutting down this interaction offers an opportunity to bolster the immune system and treat cancer.”
Other authors include Lisa M. DeCamp, Brandon M. Oswald, Ph.D., Susan M. Kitchen-Goosen, Zhen Fu, Ph.D., Matthew Vos, Shelby E. Compton, Ph.D., Joseph Longo, Ph.D., Nicole M. Foy, Kelsey S. Williams, Ph.D., Abigail E. Ellis, Amy Johnson, Ibukunoluwa Sodiya, M.S., Michael Vincent, Ph.D., Hyoungjoo Lee, Ph.D., Ryan D. Sheldon, Ph.D., and Connie M. Krawczyk, Ph.D., of Van Andel Institute; and Chen Yao, Ph.D., and Tuoqi Wu, Ph.D., of University of Texas Southwestern Medical Center.
Research reported in this publication was supported by Van Andel Institute; Van Andel Institute Metabolism and Nutrition (MeNu) Program Pathway to Independence Awards (Dahabieh and Longo); the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award nos. DP2AI154450 (Yao) and R01AI158294 (Wu); the Cancer Prevention and Research Institute of Texas under award no. RR210035 (Yao); the National Institute on Aging of the National Institutes of Health under award no. R01AG056524 (Wu); a V Scholar Award (Wu); an American Federation for Aging Grant for Junior Faculty (Wu); a Clinic & Laboratory Integration Program Grant (Cancer Research Institute) (Wu); startup funds from University of Texas Southwestern (Yao and Wu); and startup funds from University of Colorado (Wu). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other funding organizations.
###
ABOUT VAN ANDEL INSTITUTE
Van Andel Institute (VAI) is committed to improving the health and enhancing the lives of current and future generations through cutting-edge biomedical research and innovative educational offerings. Established in Grand Rapids, Michigan, in 1996 by the Van Andel family, VAI is now home to more than 500 scientists, educators and support staff, who work with a growing number of national and international collaborators to foster discovery. The Institute’s scientists study the origins of cancer, Parkinson’s and other diseases and translate their findings into breakthrough prevention and treatment strategies. Our educators develop inquiry-based approaches for K–12 education to help students and teachers prepare the next generation of problem-solvers, while our Graduate School offers a rigorous, research-intensive Ph.D. program in molecular and cellular biology. Learn more at vai.org.
END
Hepatitis B virus (HBV) infection is known to be associated with the risk of hepatocellular carcinoma (HCC), but how and why they are connected remains unknown. Researchers from Mass General Brigham discovered that HBV does not cause liver inflammation or cancer on its own, but worsens liver inflammation and may make patients more susceptible to early cancer development caused by environmental carcinogens. Limiting carcinogen exposure or reducing inflammation could mitigate this risk. The results are published in Nature Communications.
“Our research sheds light on the intricate interplay between HBV infection and carcinogen exposure to generate immune dysregulation ...
A new study by Dr Tom M. Fayle of Queen Mary University of London, Dr Kalsum M. Yusah of the Royal Botanic Gardens, Kew, and Dr Jiri Tuma of the Biology Centre of the Czech Academy of Sciences, Czech Republic, published today in the journal Soil Ecology Letters, shows the importance of old termite mounds as habitats for a wide range of insects and other invertebrates in Bornean tropical rainforest.
Termites play a critical ecological role in many ecosystems. By building and maintaining their nests and mounds, they influence soil turnover, chemical soil properties, and nutrient distribution. Once these mounds are abandoned by their original ...
Fatty liver disease, caused by the accumulation of fat in the liver, is estimated to affect one in four people worldwide. If left untreated, it can lead to serious complications, such as cirrhosis and liver cancer, making it crucial to detect early and initiate treatment.
Currently, standard tests for diagnosing fatty liver disease include ultrasounds, CTs, and MRIs, which require costly specialized equipment and facilities. In contrast, chest X-rays are performed more frequently, are relatively ...
The use of electronics in various forms is on the rise, from wearable devices like smartwatches to implantable devices like body-implanted sensors, skin-worn smart patches, and disposable monitoring devices. These devices, which are inevitably discarded after use, contribute to the growing problem of electronic waste (e-waste), a significant environmental concern.
The Korea Institute of Science and Technology (KIST) has announced that a joint research team, led by Dr. Sangho Cho of the Center for Extreme Materials Research and Dr. Yongho Joo of the Center for Functional Composite Materials Research, has developed a polymeric material ...
A groundbreaking study has revealed that small but mighty zooplankton—including copepods, krill, and salps—are key players in the Southern Ocean’s ability to absorb and store carbon.
Led by an international team of researchers, and published in Limnology and Oceanography, the study quantifies for the first time how these tiny creatures collectively enhance carbon sequestration through their seasonal, vertical migrations.
The Southern Ocean is a key region for carbon storage. Traditional thinking is that the carbon storage in the Southern Ocean is dominated by gravitational ...
A cup and a half of leafy green vegetables could go a long way to addressing atherosclerotic vascular diseases (ASVD’s), new research from Edith Cowan University (ECU), the University of Western Australia and the Danish Cancer Institute has found.
ASVDs are a subgroup of cardiovascular disease, which are current leading causes of death world-wide, primarily due to heart attacks and strokes. ECU PhD student Ms Montana Dupuy noted that in Australia, cardiovascular diseases claim the life of one person every 12 minutes.
Research led by Ms Dupuy has found that the higher dietary intake of Vitamin K1 could reduce the risk of ASVD.
“Leafy ...
Two-dimensional patterned hollow structures (2D-PHS) are an advanced class of metamaterials known for their unique mechanical properties and lightweight nature. Comprising a solid matrix with periodically arranged hollows, 2D-PHS effectively reduce material weight while optimizing stress and strain distribution to maintain structural integrity and strength. This precise geometric control offers superior tunability in strength-to-weight ratios, deformability, and stretchability compared to traditional solid ...
Groundwater input to coral reefs directly affects water chemistry and triggers a cascade of changes in the coastal ecosystem, according to a new study led by University of Hawaiʻi (UH) at Mānoa oceanographers. Freshwater from land that flows into the ocean beneath the sea surface, termed submarine groundwater discharge, was found to increase nutrient availability, change acidity of the seawater, and impact the process by which corals build their skeletons. This research, published recently in Ecological Monographs, provides critical insights into the complex interactions between the land and ocean.
“Submarine groundwater discharge is a widespread and ...
To make advances in using microbes to sustainably produce materials, it is necessary to find new molecular tools, or “enzymes” — but this is labor intensive. A Kobe University team now developed a technique that can classify thousands of candidates and a workflow that can evaluate representatives overnight, in what may become a fundamental technology for biomanufacturing.
As oil reserves dwindle and prices soar, microorganisms can help us produce useful chemicals and fuels from renewable resources. They can convert raw materials ...
The accumulation of plastic waste worldwide poses a serious threat to wildlife and ecosystems. Catalytic processes that convert plastic waste into valuable chemicals and fuels offer a promising solution. However, real-life plastic waste mixtures have highly diverse composition and structural complexity, and accurate identification of the components within the mixtures is a prerequisite for their effective separation and recycling.
In a study published in Nature, Prof. XU Shutao from the Dalian Institute of Chemical Physics (DICP) of the Chinese Academy of Sciences, in collaboration with the team of Prof. WANG Meng and Prof. MA Ding from Peking University, developed ...
