A New Risk Score May Improve Predicting Mantle Cell Lymphoma Outcomes

Mantle cell lymphoma (MCL) is a type of blood cancer that can behave very differently from person to person. Some people respond well to treatment for many years, while others relapse sooner. Because of this, doctors rely on risk tools to estimate how aggressive the lymphoma may be. A new study presented at the 2025 ASH meeting suggested that looking at the immune environment around the lymphoma may give clearer answers. 

Why better risk tools are needed for MCL

At diagnosis, many people with MCL want to know what to expect. Doctors often look at genetic changes of MCL cells to estimate risk. One important marker is TP53, a gene that helps control cell growth. Changes in TP53 are linked with poorer outcomes.

Another commonly used tool is the “proliferation signature,” which measures how fast lymphoma cells are dividing. While helpful, these tools do not explain all differences in outcomes. This study aimed to find additional markers that could better predict survival for people with MCL. 

The new immune signature 

Researchers used data from the Atlas of Blood Cancer Genomes project, an international effort studying blood cancers in detail. Tumor samples from 252 people with MCL were analyzed using advanced sequencing methods that look at DNA and RNA. They tested whether different gene patterns could predict patients’ outcomes. 

The researchers identified a new pattern called an “immune signature.” A gene expression signature is a group of genes whose activity levels give information about how a cancer behaves.

This immune signature was different from the older proliferation signature. It focused on genes linked to the tumor microenvironment, meaning the immune cells that live in and around the lymphoma. In particular, it reflected levels of CD8+ T cells and T follicular helper cells, which are immune cells involved in controlling cancer.

Patients labeled as high-risk by the immune signature had fewer of these helpful immune cells in their tumor environment.

Identifying clearer risk groups for MCL

Across all patients, the immune signature separated people into clear risk groups. Five years after diagnosis:

• 91% of people with a low-risk immune score were alive
• 80% of people with an intermediate-risk immune score were alive
• 45% of people with a high-risk immune score were alive

Importantly, the immune signature worked even when TP53 status was considered. Among people without TP53 changes, those with a high-risk immune score had a lower overall survival than those with a low-risk immune score. The same pattern was seen in people with TP53 changes, where outcomes ranged from very poor to quite favorable depending on the immune score. 

The immune signature also helped refine risk for people already labeled as high-risk by the proliferation signature. This means it added useful information rather than repeating what doctors already knew. 

What this means for patients

These findings suggest that the immune environment plays a major role in how MCL behaves. A test based on this immune signature could one day help doctors better estimate risk at diagnosis and tailor follow-up or treatment strategies.

More research is needed before this approach becomes part of routine care. Future studies will also explore whether differences in immune cells could guide choices about therapies. If you have questions about tests for MCL, please contact your MCL specialist. 

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Source: 

• Novel immune gene expression signature risk-stratifies mantle cell lymphoma outcomes independent of TP53 status