Gene expression patterns could help explain why some patients don’t respond well to anti-rejection therapies
PHOENIX (Aug. 10, 2026) — A new study published today found that when the body rejects a transplanted heart, the changes happening inside the cells are more complex than what doctors can see with standard biopsy images.
The findings by researchers at TGen, part of City of Hope, and Vanderbilt Health could help clinicians understand why patients with the same levels of rejection severity, based on biopsy histology, may have different outcomes. It may also help explain why patients respond differently to anti-rejection immune treatments.
“A lot of information just can’t be captured by image data alone. Having this extra layer of molecular information adds a new tool for determining outcomes,” said Nicholas Banovich, Ph.D., professor and director of the Division of Bioinnovation and Genome Sciences at TGen and a senior author of the study. “This doesn’t replace a pathologist’s expertise in evaluating tissue samples and determining what’s happening. Instead, it provides additional insights that can support prognosis and help guide treatment decisions.”
Of the more than 4,500 cardiac transplants annually in the U.S., up to 35% experience rejection within a year of their procedure. There are two main types of rejection: acute cellular rejection, in which a patient’s T cells attack the heart, and antibody-mediated rejection, where antibodies are the culprit. While common, these episodes can contribute to long-term failure of the transplant and death by predisposing transplant patients to chronic rejection conditions such as cardiac allograft vasculopathy (CAV).
In their study published in Nature Cardiovascular Research, Banovich and colleagues used spatial transcriptomics to map gene expression at the subcellular level in a series of cardiac tissue biopsies taken from 62 adult and child heart transplant patients. Every transplant patient is biopsied regularly and routinely over time to monitor the heart for rejection.
“Traditionally, tissue samples from these biopsies have been evaluated using histology to diagnose and grade rejection. However, there is considerable heterogeneity from one sample to another, making consistent interpretation a challenge,” explained Kaushik Amancherla, M.D., assistant professor of medicine at Vanderbilt Health and co-first author of the study. “Our goal was to use spatial technology to better understand the molecular and cellular features of acute rejection, recovery, and long-term outcomes.”
“We were able to identify and map the spatial organization of immune and cardiac cell types involved in rejection,” said Angela Taravella Oill, Ph.D., a TGen computational scientist and co-lead author of the study.
Oill and colleagues identified differentially expressed genes between the two types of acute rejection but found broad overlap in gene expression states across different levels of rejection severity. There were even differences in expression patterns within the same rejection severity grade. They also identified cell-type resolved gene expression patterns associated with CAV.
When the team examined baseline rejection biopsies, they found that patients who responded to immune-modulating anti-rejection drugs had gene expression profiles different from those in patients who did not respond.
“One of the most exciting findings was the potential to identify biomarkers that could one day help predict which patients are more likely to respond well to specific therapies,” said Oill. “We found several meaningful correlations between certain cell types, gene expression patterns, and patient outcomes. The next step is determining whether these biomarkers can reliably predict outcomes across larger patient populations.”
The International Society for Heart and Lung Transplantation Enduring Hearts Transplant Longevity Award, the American Heart Association, the Red Gates Foundation, and the National Institutes of Health (grant K23HL166960) supported this research.
About TGen, part of City of Hope
Translational Genomics Research Institute (TGen) is a Phoenix, Arizona-based nonprofit organization dedicated to conducting groundbreaking research with life-changing results. TGen is part of City of Hope, a world-renowned independent research and treatment center for cancer, diabetes and other life-threatening diseases. This precision medicine affiliation enables both institutes to complement each other in research and patient care, with City of Hope providing a significant clinical setting to advance scientific discoveries made by TGen. TGen is focused on helping patients with neurological disorders, cancer, diabetes and infectious diseases through cutting-edge translational research (the process of rapidly moving research toward patient benefit). TGen physicians and scientists work to unravel the genetic components of both common and complex rare diseases in adults and children. Working with collaborators in the scientific and medical communities worldwide, TGen makes a substantial contribution to help patients through efficiency and effectiveness of the translational process.
TGen Media Contact
Galen Perry
602-343-8423
gperry@tgen.org
SOURCE: Pres Release