Researchers have discovered that type II innate lymphoid cells (ILC2s), which are a type of immune cell, can alter their properties and functions when a cancer patient receives donor stem cells. This change can hinder the successful and healthy rebuilding of the immune system. This new insight into the adaptability of ILC2 cells could inform more effective methods for improving immune recovery after transplants and potentially enhance the outcomes for those receiving such treatments.
Researchers at UNC Lineberger Comprehensive Cancer Center, alongside their colleagues, have found that a specific group of immune cells known as type II innate lymphoid cells (ILC2s) can modify their characteristics and functions following a cancer patient’s receipt of donor stem cells. This alteration may hinder the effective restoration of a healthy immune system. Understanding the adaptable nature of ILC2 cells may lead to improved strategies for bolstering immune recovery following transplantation.
The study was published on July 17, 2024, in Nature Communications.
In the United States, over 8,000 allogeneic stem cell transplants have been performed yearly over the past decade. This procedure, which involves infusing healthy cells from a donor into a patient, is commonly used to treat various cancers, including acute lymphoblastic and acute myelogenous leukemias, myelodysplastic syndromes, and certain lymphomas.
“Allogeneic transplants can be quite effective and possibly lifesaving. However, not every immune cell transferred to a recipient is derived from the donor,” explained Jonathan Serody, MD, the corresponding author and Elizabeth Thomas Professor of Medicine, Microbiology and Immunology, chief of hematology at UNC School of Medicine, and director of the UNC Cellular Therapy Program. “After transplantation, innate type 2 lymphoid cells often do not proliferate effectively in the recipient, with those ILC2s deviating from their original programming leading to more complications post-transplant, making them our focal point.”
The success of allogeneic stem cell transplants relies on several factors, including the patient’s remission status, their age, and the compatibility between the patient’s and donor’s human leukocyte antigens (HLAs). HLAs are proteins present on most cells, and a closer match between HLAs increases the likelihood of success while reducing the risk of post-transplant complications such as graft-versus-host disease, where donor immune cells attack the recipient’s tissues.
Serody highlighted that understanding the influence of ILC2s on transplant success and ways to modify this influence could be crucial for patient treatment.
The majority of the experiments conducted by the researchers were performed on mice, with additional tests on samples from 12 cancer patients at the Duke Cancer Institute in Durham, North Carolina. In the mouse studies, over 80% of the ILC2 cells transplanted into mice transitioned to an ILC1-type after 20 days. This unexpected change has the potential to exacerbate graft-versus-host disease.
Through the mouse studies, researchers were able to pinpoint, at the single-cell level, the genetic composition of each cell, as well as how proteins and DNA interacted within the cell’s nucleus. These factors can influence gene expression, which can ultimately impact transplant results.
“Our method has unveiled the identities of cells within a complex transplant environment, which could facilitate the development of new therapeutic strategies,” noted Ian Davis, MD, PhD, a co-author of the study, chief of pediatric hematology-oncology, and Stuart H. Gold Professor of Childhood Cancer at UNC School of Medicine. “We hope to create future therapies that guide the recovery of the immune system towards immune cell types associated with better outcomes following transplantation.”
The researchers are initiating a clinical trial to assess whether infusing ILC2 cells can help mitigate lower gastrointestinal graft-versus-host disease. If deemed safe, they may genetically modify ILC2 cells to enhance their efficacy in a subsequent study.
Serody emphasized that the collaborative nature of research on graft-versus-host disease conducted in his lab alongside the work in Davis’s lab focusing on gene transcription modulators in cancer is unique compared to practices at many other institutions. “This level of collaboration has enabled this significant research discovery to rapidly reach fruition,” Serody stated.
The primary authors of the paper are Sonia J. Laurie, PhD, a postdoctoral fellow in the Serody lab at UNC Lineberger, and Joseph P. Foster II, a graduate student in the Davis lab at UNC Lineberger.
