A new study published in The Journal of Immunology by researchers at the Josep Carreras Leukaemia Research Institute (IJC) has uncovered a crucial biological “off switch” in diffuse large B cell lymphoma (DLBCL), the most common and one of the most aggressive forms of blood cancer. The findings reveal that a protein called HDAC7 plays a dual role: it is essential for building a healthy immune system, and when it goes missing in cancer cells, the disease becomes significantly more dangerous . Crucially, the team showed that restoring HDAC7 in cancer cells can slow or even stop tumor growth.
DLBCL is a cancer of the immune system’s B cells which normally are responsible for producing the antibodies that protect us from infections. It is the most common type of non-Hodgkin lymphoma, accounting for roughly 40% of all diagnoses worldwide. While some patients respond well to standard chemotherapy (known as R-CHOP), a significant proportion do not, and identifying who is at risk of a poor outcome remains one of the major challenges in treating the disease.
When our immune system encounters a new virus or a bacterium, B cells rush to specialized structures inside our lymph nodes called germinal centers. Think of these as intensive training academies: inside them, B cells multiply rapidly, learn to recognize the enemy with ever-greater precision, and graduate as highly effective antibody factories. This process is essential for a robust immune response.
The IJC team, led by Dr Maribel Parra and researchers Ainara Meler and Mar Gusi-Vives , found that HDAC7 acts as a master controller of this training process. In mouse experiments, when the HDAC7 protein was removed from B cells, the cells could not complete their training: they became stuck in an early, immature state, failed to produce the right antibodies, and could not graduate into fully functional immune defenders. In short, without HDAC7, the immune system’s training academy breaks down.
The researchers then asked what happens to HDAC7 in DLBCL. When they examined tumor samples from patients, many of them expressed lower levels of this key regulatory factor. Moreover, when analyzing survival data from 292 DLBCL patients, the team found that patients whose tumors had low levels of HDAC7 had a significantly worse prognosis than those whose tumors retained more normal levels of the protein. In other words, HDAC7 behaves like a natural brake on the cancer: when it is lost, the disease accelerates.
The most promising finding came from laboratory experiments in which the team artificially restored HDAC7 expression in DLBCL cancer cells. The effect was dramatic: the cancer cells stopped multiplying and began to die, and tumors shrank significantly when HDAC7 was switched back on.
These results suggest that HDAC7 functions as a natural tumor suppressor, a biological safeguard that normally keeps B cell proliferation in check, and whose loss contributes directly to cancer development and progression.
This discovery has two immediate and practical implications for people affected by DLBCL.
First, measuring HDAC7 levels in a patient’s tumor could serve as a new biomarker — a molecular signal that helps doctors predict how the disease will behave and tailor treatment accordingly. This is a step toward more personalized, precision medicine for blood cancer patients.
Second, the fact that restoring HDAC7 kills cancer cells in the laboratory suggests it could become a future therapeutic target. If scientists can identify why HDAC7 is lost in tumors and find ways to switch it back on, it may open the door to novel treatments for patients who do not respond to current therapies.
The Josep Carreras Institute is dedicated to curing blood cancers — and curing them requires both better ways to predict how a cancer will behave and new treatments for patients who don't respond to existing ones. Although further confirmatory studies are required, this study has potential to advance on both fronts: it identifies a molecular signal, HDAC7, that could tell clinicians at diagnosis how aggressive a patient's DLBCL tumor is likely to be; and it shows that restoring this particular signal in cancer cells stops tumor growth, which could point the way towards therapeutic interventions that target this pathway.
“This work identifies HDAC7 as both a guardian of normal immune cell development and a potential suppressor of lymphoma. We believe it can help us classify patients more precisely and, in the longer term, design new therapeutic strategies specifically tailored to those who need them most.”
Dr Maribel Parra , Principal Investigator, Lymphocyte Development and Disease Group, Josep Carreras Leukaemia Research Institute.
The Journal of Immunology
Experimental study
Human tissue samples
“HDAC7 is a key factor for the germinal center reaction and its underexpression is associated with DLBCL prognosis”
18-Mar-2026