In August 2020, scientists at the Cancer Research Institute of the University of Montpelier in France published a comprehensive study of the tumor microenvironment of primary central nervous system diffuse large B-cell lymphoma (PCNSL) on the preprint server bioRxiv.1 The study, which has not yet undergone peer review, shows that the microenvironment — or benign immune cells in the tumor — of PCNSL can be split into 3 subgroups: immune rich, immune poor, and immune intermediate. The findings may open the door to new options for treatment.

“What’s interesting about this study is that it focuses on the immune environment and shows that you have these immune rich vs immune poor and then something in between as 3 kind of types of primary CNS lymphomas,” said Stephen Ansell, MD, PhD, hematology researcher who specializes in B-cell malignancies at the Mayo Clinic in Rochester, Minnesota.

Dr Ansell says that it is the hope of scientists and oncologists that that characterizing the microenvironment will help doctors match cancer types to treatments. Immune-rich or “hot” cancers are treated very differently than immune-poor or “cold” ones.

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According to Siba El Hussein, MD, hematopathologist at MD Andersen Cancer Center, Houston, Texas, characterizing the tumor microenvironment has become a “trendy topic” over the past 5 years. The research is concurrent with the growth of target immunotherapies, like chimeric antigen receptor T-cell (CAR-T) therapies and checkpoint inhibitors, that use the patient’s own immune cells to fight cancer. “We’re not only targeting cancer cells anymore, we’re also kind of jumping to the next level and helping the microenvironment fight against cancer,” she said.

But there is still very little known about this rare form of aggressive non-Hodgkin lymphoma. Its median survival rate is 30 to 50 months2 and approximately 50% of people experience disease recurrence. Today, the first line of treatment is a broad-acting high-dose methotrexate. About 10% to 15% of patients develop primary refractory disease. These poor outcomes underscore the need for better understanding of the cancer so PCNSL can benefit from precision therapies.

Research on PCNSL has lagged behind because it is a very rare cancer, comprising only 4% of brain cancers. Adding to that hurdle is its location in the brain, which makes it difficult to obtain tissue samples.

But in 2017, research from the lab of Margaret Shipp, MD, at Dana-Farber Research Institute, Boston, Massachusetts, shed some light on its genetics that could inform treatment decisions.1