University research promotes new therapeutic strategies against non-Hodgkin's lymphoma

A team of researchers from the University of Navarra, in partnership with the pharmaceutical business Roche, the Instituto de Salud Carlos III-CIBERONC, the University of Salamanca, and the Instituto de research Sanitaria de Navarra (IdisNA), has made a core topic finding in the biology of diffuse large B-cell lymphoma (DLBCL), the most frequent subtype of non-Hodgkin's lymphoma.

DLBCL lymphoma is an aggressive cancer affecting B lymphocytes, characterized by diffuse growth in lymphoid tissues (such as lymph nodes and spleen) and a heterogeneous clinical course. Without treatment, its progression is rapid and with negative consequences for the health of patients, and although current immunochemotherapy allows remission in many patients, a significant percentage experience relapses or develop resistance, which underlines the need for new therapeutic strategies. This subject of tumors corresponds to the most frequent subtype of non-Hodgkin's lymphoma, representing approximately 30-40% of these cases and between 5-20% of total hematological malignancies.

The study, published in Blood, one of the most prestigious international scientific journals in hematology, reveals the crucial role of interleukin-10 (IL-10), secreted by tumor B cells, in disease progression and in the remodeling of the tumor microenvironment. This mechanism of communication through IL-10 turns out to be fundamental for the success of emerging immunotherapy strategies. The findings open new therapeutic possibilities for this highly aggressive lymphoma, with a potential impact on the development of more effective immunotherapies.

New forms of immunotherapy

The researchers developed an immunocompetent animalmodel that recreates this human disease, in which they were able to knock out the IL-10 gene specifically in tumor cells. This led to the discovery that tumor IL-10 plays a dual role. On the one hand, it promotes lymphoma growth and reduces the efficacy of conventional anti-CD20 therapy. At the same time, however, it maintains a more robust anti-tumor immune response, allowing it to benefit from other types of immunotherapies, such as PD-1 blockade.

Sergio Roa, researcher at the Cancer Center Clínica Universidad de Navarra and professor at the School of Sciences of the academic institution, explains that "the preclinical programs of study have result fundamental in understanding how the secretion of IL-10 by tumor B cells not only favors their survival, but also regulates the microenvironment of the lymphoma. This mechanism prevents the tumor environment from becoming a hopelessly dysfunctional and extremely immunosuppressive niche, affecting the efficiency of new forms of immunotherapy against these lymphomas".

In addition, the researchers identified transcriptomic footprints associated with IL-10-mediated cell-cell communication, which allow predicting the clinical response of patients with DLBCL to standard immunochemotherapy treatment, called R-CHOP. The study of these footprints could improve risk stratification and facilitate the personalization of treatments, thus optimizing therapeutic outcomes. "This finding highlights the importance of the immunomodulatory role of IL-10, which leaves a footprint in the tumor that we can track at the genetic level and use to predict clinical response in patients with diffuse lymphoma," comments Dr. Marcos Garcia-Lacarte, first author of the study.

Sara Contreras, predoctoral researcher and co-author of the study, adds that "the stratification of patients according to their IL-10 production capacity and the Degree immune depletion in the tumor microenvironment opens the door to refining future strategies with new generations of immunotherapy and even improving the efficacy of current therapies".

This work not only provides fundamental insights into the biology of DLBCL lymphoma, but also provides innovative animal models for the development and assessment of new therapeutic strategies, with potential application in clinical trials.

reference letter bibliographic

Garcia-Lacarte M & Grijalba S C et al. (2025) IL-10 from tumoral B cells modulates the diffuse large B-cell lymphoma microenvironment and response to immunotherapy. Blood. (blood.2024025755). doi: 10.1182/blood.2024025755.