A new study led by BC Cancer researchers shows that classic Hodgkin lymphoma (CHL) is not one disease, but several biologically distinct subtypes. The study, published in Cancer Discovery, a journal of the American Association for Cancer Research, shows each disease subtype is caused by different genetic changes and interacts uniquely with the immune system.
“By defining biologically meaningful subtypes, we can better understand the differences in tumour behaviour and immune response. This can help us decide which therapy to use by matching treatments to specific subtypes,” says the study’s lead author Dr. Tomohiro Aoki, clinician scientist at Princess Margaret Cancer Centre and former postdoctoral fellow at BC Cancer.
The research team developed a new classification system, called HLGen, which identifies four CHL subtypes: CST, CN913, STB and CN2P. These subtypes differ in their genetic features, tumour behaviour and immune cell environments. For example, the CST subtype shows genetic changes that lead to release of TARC, a specific signaling molecule for cellular communication. The resulting induction of an immune-suppressive tumour environment allows the cancer to evade being attacked by immune cells.
“This work challenges the traditional view of Hodgkin lymphoma as one uniform disease,” adds Dr. Christian Steidl, principal investigator of this study, executive director, research at BC Cancer, and professor, pathology and laboratory medicine at the University of British Columbia.
To identify these subtypes of CHL, researchers combined advanced imaging technologies with detailed genetic and molecular profiling, allowing them to study the cancer cells themselves and how they interact with surrounding immune cells.
This work builds on earlier Hodgkin lymphoma classifications by creating more biologically meaningful subtypes that integrate genetics, tumour biology and the immune landscape. The findings were presented at the International Symposium on Hodgkin Lymphoma in 2024, where they were recognized with the Karl Musshoff Prize.
The HLGen classification system is designed to be used by the research community to support further studies and clinical trials that match patients to therapies based on the molecular and immune features of their disease.
The study was supported by generous donations to the BC Cancer Foundation, as well as funding from the Terry Fox Research Institute, Canadian Cancer Society, Genome Canada and Genome BC.