Liver cancer ranks as the fourth deadliest cancer in Hawaiʻi, posing a significant threat to the local population, particularly affecting Native Hawaiian, Filipino, and Japanese men. The progression of liver cancer, with its potential for liver failure when tumours metastasize, has been a cause for concern, as it can lead to a rapid decline in health and even death.
While immunotherapy has become the standard of care for cancer treatment, its efficacy in liver cancer has been limited, prompting a team of researchers led by Benjamin Green at the University of Hawaiʻi Cancer Center to delve into this issue.
Immunotherapy, which leverages a person’s immune system to combat cancer, has proven successful in slowing the spread of many types of cancer. However, liver tumours have often remained unresponsive to this treatment, leaving patients with limited options. Benjamin Green and his team aimed to uncover the reasons behind this resistance to immunotherapy in liver cancer.
One of the challenges they identified was the generation of pro-cancer immune cells known as regulatory T cells, or “Tregs,” by immunotherapy. These Tregs can suppress the immune response, hindering the body’s ability to fight cancer effectively. To better understand this phenomenon, Green and his team utilized cutting-edge sequencing technology and conducted a comprehensive analysis of liver Tregs in mice subjected to immunotherapy.
Their groundbreaking research revealed that liver Tregs expressing a specific protein, CD29, exhibited heightened immunosuppressive capabilities. Furthermore, the abundance of these CD29+ Tregs increased when mice received immunotherapy, regardless of the type of cancer introduced into the liver. The CD29 protein’s role in regulating the Treg population in the liver, while understudied, appeared to have a significant impact.
Green emphasized the broader implications of their findings, stating that “Our results may be applicable to a range of liver diseases. In liver cancer, we think that CD29 may represent a new potential drug target to help patients respond to immunotherapy.” This discovery opens the door to the possibility of developing new drugs that target CD29+ Tregs, potentially improving the effectiveness of immunotherapy in liver cancer treatment.
To further validate their findings and explore the relevance of CD29+ Tregs in local patients, Green has initiated a collaboration with data scientists and molecular pathologists at the UH Mānoa John A. Burns School of Medicine, along with liver cancer doctors at The Queen’s Medical Center. Together, they aim to examine a range of liver tumours removed from both Hawaiian and non-Hawaiian patients to determine if these tumours contain varying percentages of CD29+ Tregs.
The implications of this research are far-reaching. If CD29+ Tregs are indeed a key factor in liver cancer resistance to immunotherapy, it could revolutionize treatment strategies for liver cancer not only in Hawaiʻi but worldwide. The potential for targeted therapies that address these immunosuppressive Tregs opens new avenues of hope for patients battling this devastating disease.
As Benjamin Green and his team continue their work, the medical community eagerly anticipates the possibility of more effective treatments that can transform the outlook for liver cancer patients, particularly in regions where the disease poses a significant threat.
The collaboration between researchers, pathologists, and medical professionals in Hawaiʻi is not only advancing scientific knowledge but also offering a ray of hope for those affected by this deadly cancer. Liver cancer may be the fourth deadliest cancer in Hawaiʻi, but with innovative research and the dedication of scientists like Green, there is a strong sense that this status could change soon.
Reference
Benjamin L Green et al, Immunosuppressive CD29+Treg accumulation in the liver in mice on checkpoint inhibitor therapy, Gut (2023). DOI: 10.1136/gutjnl-2023-330024.
