Many patients with an aggressive blood cancer called diffuse large B-cell lymphoma are cured with the current gold standard treatment: a combination of antibodies designed to wipe out cancerous B cells and four chemotherapy drugs. However, this treatment fails in about three out of 10 patients, and the powerful chemotherapy can cause heart damage, a significant risk for older patients, who make up the majority of those diagnosed.
Despite these risks, clinicians are often reluctant to try new treatment regimens that may be less toxic because there is no reliable way to predict whether a patient’s cancer will respond.
A new study of pet dogs treated with a promising new treatment for the same cancer suggests that immune signatures found in blood samples could help identify poor responders early. The findings of this study were announced today. scientific reportpoints to a future where blood tests can help guide more personalized treatment decisions, both in veterinary medicine and human cancer treatment.
For this study, researchers at Tufts University Cummings School of Veterinary Medicine and Massachusetts Chan School of Medicine analyzed blood samples taken during previous clinical trials of pet dogs being treated for diffuse large B-cell lymphoma.
In that trial, dogs were randomly assigned to one of three new treatment regimens. Each regimen combined canine antibodies equivalent to those used in human medicine with a low dose of doxorubicin, one of four traditional chemotherapy drugs (a milder version of the gold standard of treatment), followed by one of three experimental immune-boosting therapies. (Two of these new immunotherapies are currently being tested in humans as well.)
Rather than focusing on tumor tissue, the researchers looked at gene activity in immune cells circulating in the dogs’ blood. It’s a non-invasive approach similar to liquid biopsies, which are increasingly used in human and veterinary oncology. Blood samples were analyzed at several key time points. Before antibody treatment and chemotherapy were started. Seven days into the treatment regimen, just before administering the new immunotherapy. At the end of a chemoimmunotherapy cycle. and finally, either when the cancer returns or 400 days after treatment if the dog is cancer-free.
The researchers then compared the patterns of gene activity in dogs whose cancer returned quickly and those that survived much longer after treatment.
Many of today’s cancer treatments are designed to strengthen the immune system to help eliminate tumors. What we discovered was that certain immune-related genes circulating in the blood are associated with better or worse response to treatment. ”
Gillian Richmond, assistant professor of comparative pathobiology at the Cummings School and one of three senior authors on this study
Researchers found that the activity of two genes, CD1E and CCL14, was associated with long-term survival. CD1E helps transmit molecular signals that allow T cells to better recognize and attack cancer, while CCL14 acts like a chemical beacon, helping recruit immune cells to where they are needed.
Professor Richmond said this suggested the two genes could act as blood-based markers of a more effective immune response to treatment. The researchers found that it didn’t seem to matter which immunotherapy the dog was receiving. Rather, the outcome appears to depend on whether the immune system is already depleted before treatment begins.
One of the most surprising findings concerned an interferon-stimulated gene, which was consistently associated with worse outcomes in dogs, including shorter survival and earlier recurrence. “Interferon is a type of cytokine, a protein that immune cells use to talk to each other and coordinate their responses,” Professor Richmond explained. “Historically, in oncology, the interferon response has been thought of as primarily protective, because it tells the immune system to fight cancer.”
“However, our results suggest that in blood cancers like lymphoma, some interferon-related signals may actually be harmful,” she said. “In this context, we suspect they may be helping cancerous blood cells survive or continue to proliferate rapidly.”
The researchers also identified three genes, TBHD, NPNT, and ISG20, whose activity could predict poor outcome as early as one week after starting treatment. Co-senior author Heather Gardner, assistant professor and Yousen Professor of Family Career Development in the Cummings School, developed a simple clinical test that can detect increased activity of these genes associated with decreased survival.
The findings suggest that a rapid blood test early in treatment could flag dogs at high risk of cancer recurrence, allowing veterinarians to adjust treatment sooner. Co-senior authors Cheryl London, Anne Engen, and Dusty, professor of comparative oncology at the Cummings School, will evaluate whether using this blood test to guide treatment decisions could ultimately improve survival rates for dogs with lymphoma.
“Our long-term goal is to use the data we have obtained in dogs with lymphoma to develop new diagnostic and therapeutic combinations that can be successfully applied to human lymphoma patients to reduce treatment-related toxicities and improve outcomes,” Professor London said.
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Reference magazines:
Rao, K. Others. (2026). Peripheral blood mononuclear cell gene expression signature predicts long-term survival in canine DLBCL. scientific report. DOI: 10.1038/s41598-026-44677-0. https://www.nature.com/articles/s41598-026-44677-0
