Blood Tests Predict Lymphoma Treatment Response in Dogs – and Humans

A simple blood test could one day facilitate doctors determine whether a patient’s aggressive lymphoma will respond to standard treatment, potentially sparing some individuals from the harsh side effects of chemotherapy. New research, initially conducted in dogs with lymphoma, reveals that analyzing immune signatures in blood samples may predict treatment response, offering a path toward more personalized cancer care.

Diffuse large B-cell lymphoma (DLBCL) is a common type of aggressive blood cancer. While the current standard treatment – an antibody combined with four chemotherapy drugs – is effective for many, it fails in roughly three out of ten patients and carries a significant risk of heart damage, particularly for older individuals who comprise a large portion of those diagnosed. Clinicians often hesitate to explore newer, less toxic treatments due to the lack of reliable methods to predict which patients will benefit.

Immune Signatures as Predictors

The study, published in Scientific Reports, focused on canine lymphoma, which shares many characteristics with the human disease. Researchers at Cummings School of Veterinary Medicine at Tufts University and UMass Chan Medical School analyzed blood samples from dogs undergoing treatment with novel regimens for DLBCL. The dogs received a canine antibody similar to those used in human medicine, a lower dose of doxorubicin (a traditional chemotherapy drug), and one of three experimental immune-boosting therapies. Two of these immunotherapies are now also being tested in human clinical trials.

Instead of examining tumor tissue directly, the team focused on gene activity within immune cells circulating in the dogs’ blood – a technique akin to “liquid biopsies” increasingly used in both human and veterinary oncology. Blood samples were collected at multiple points throughout treatment: before starting, seven days in, just before immunotherapy, at the end of the cycle, and either upon cancer recurrence or 400 days post-treatment if the cancer remained in remission. By comparing gene activity patterns between dogs with successful and unsuccessful treatment outcomes, researchers identified potential biomarkers.

Key Genes and Immune Response

The research highlighted the importance of two genes, CD1E and CCL14, which were linked to long-term survival. CD1E plays a role in enabling T cells to recognize and attack cancer cells, while CCL14 acts as a signal to attract immune cells to the tumor site. According to Jillian Richmond, an assistant professor of comparative pathobiology at Cummings School and a senior author on the study, these genes could serve as blood-based markers of a more effective immune response to therapy.

Interestingly, the type of immunotherapy administered didn’t seem to be the determining factor. Instead, the study suggested that the state of the immune system *before* treatment began was more crucial. Dogs whose immune systems were already “exhausted” appeared less likely to respond positively.

The Unexpected Role of Interferon

One of the most surprising findings involved interferon-stimulated genes. Traditionally, interferon responses have been considered protective in cancer treatment, signaling the immune system to fight the disease. However, this study found that activity in these genes was consistently associated with worse outcomes in dogs, including shorter survival times and earlier relapse.

“Our results suggest that in a blood cancer like lymphoma, some interferon-related signals may actually be harmful,” explains Richmond. “We suspect that, they may be helping cancerous blood cells survive or continue to rapidly reproduce.” This challenges conventional understanding and opens new avenues for research into the complex interplay between interferon and lymphoma progression.

A Potential Early Warning System

The researchers also identified three genes – TBHD, NPNT, and ISG20 – whose activity levels just one week into treatment appeared to predict a poor outcome. Heather Gardner, a professor at Cummings School, developed a laboratory test to detect elevated activity in these genes, potentially flagging dogs at higher risk of cancer recurrence. This rapid blood test could allow veterinarians to adjust treatment plans sooner, potentially improving outcomes.

Canine lymphoma, as described in Frontiers in Veterinary Science, is a common aggressive B-cell lymphoma in dogs, and recent molecular investigations have shown it’s a heterogeneous tumor, meaning it presents differently in various cases. This complexity underscores the necessitate for more personalized treatment approaches.

Translating Findings to Human Cancer Care

Cheryl London, a professor in comparative oncology at Cummings School, plans to evaluate whether using this blood test to guide treatment decisions can ultimately improve survival rates in dogs with lymphoma. The ultimate goal, however, is to translate these findings to human patients.

“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,” says London. This approach, known as comparative oncology, recognizes the similarities between cancers in humans and animals, allowing researchers to accelerate the development of new treatments.

What’s Next: Refining the Biomarkers and Clinical Trials

The research team is now focused on refining the identified biomarkers and conducting larger clinical trials to validate their predictive power. Further studies will be needed to determine the optimal timing and frequency of blood tests, as well as to identify other potential biomarkers that could further improve treatment selection. The team also intends to investigate the mechanisms by which interferon-stimulated genes contribute to lymphoma progression, potentially leading to the development of new therapies that target these pathways. The findings from Tufts University build on earlier research indicating that simple blood tests may predict response to lymphoma treatment, offering hope for a future of more personalized and effective cancer care.