A new study published in Scientific Reports on Mar. 25 suggests that immune signatures found in blood samples may help predict which patients with diffuse large B cell lymphoma will respond to treatment. Researchers from Cummings School of Veterinary Medicine at Tufts University and UMass Chan Medical School analyzed blood samples from pet dogs treated for this aggressive form of blood cancer, aiming to identify early markers of poor response.
Diffuse large B cell lymphoma is commonly treated with an antibody and a combination of four chemotherapy drugs, but about 30 percent of patients do not respond to this regimen. The intense chemotherapy can also cause heart damage, especially in older patients. Clinicians are hesitant to use newer treatments due to the lack of reliable predictive tools.
The research team examined gene activity in immune cells circulating in the dogs' blood at several stages during treatment. They found that two genes, CD1E and CCL14, were associated with longer survival after therapy. "CD1E helps deliver molecular signals that enable T cells to better recognize and attack cancer, while CCL14 acts like a chemical beacon, helping recruit immune cells to where they're needed," said lead researcher Richmond.
Another finding was that high activity in interferon-stimulated genes correlated with worse outcomes for the dogs studied. "Interferon is a type of cytokine, a protein that immune cells use to talk to each other and coordinate their responses," Richmond explained. "Historically in oncology, we've thought of interferon responses largely as protective... But our results suggest that in a blood cancer like lymphoma, some interferon-related signals may actually be harmful," she said.
The researchers also identified three genes—TBHD, NPNT, and ISG20—whose elevated activity one week into treatment predicted poorer outcomes. Heather Gardner developed a laboratory test capable of detecting increased activity among these genes early on.
Co-senior author Cheryl London plans further studies using this rapid blood test to see if adjusting treatments based on early results can improve survival rates for dogs with lymphoma. "Our long-term goal is to leverage the data we are generating in dogs with lymphoma to develop new diagnostics and therapeutic combinations that can be successfully translated into human lymphoma patients to reduce treatment-related toxicities and improve outcomes," said London.
