Lymphomoids: A lab model of lymphoma tumors

Cancer is a multi-faceted systemic disease that possesses certain issues that make it very challenging to treat for many reasons. Difficult treatment decision-making falls under a wide spectrum, of which lymphoma is a blood-based cancer originating from immune cells known as lymphocytes that defend the body against infections just one.

Most notably, this innovative ex vivo model, still called lymphomatoids, is proposed as a platform for personalized lymphoma treatment and is a significant milestone in the unceasing quest for better therapies.

Their insights inform traditional approaches to evaluating treatment response in lymphoma, namely, human xenograft models by using animal models. PDX models are slow, expensive, and inadequate since they barely capture the complex immune and tumor cell interactions despite the insightful data they may produce.

More recently, a device known as a tumor avatar- a trick to maintain patient-derived cells or tissues outside the body-has become quite the favorite among scientists. However, keeping the original composition and shape of lymphoma cells in these models has proven to be a major challenge.

In partnership with physicians at the Centre Hospitalier Universitaire Vaudois (CHUV), researchers at the École Polytechnique Fédérale de Lausanne (EPFL), under the direction of Drs. Albert Santamaria-Martínez and Elisa Oricchio have created a novel remedy: the lymphoid model.
Thanks to this sophisticated ex vivo model, the tumor’s architecture, cellular variety, and microenvironments—essential elements sometimes lost in conventional models—can be preserved in lymphoma tissue fragments outside the body for a few days.

Attacking lymphoma at the source

Using imaging-based analyses and spatial genetic profiling, the team collected 27 human lymphoma samples to show that lymphomas might preserve the phenotypic and molecular features of the original malignancies.

The findings were encouraging: the lymphoma tissue samples maintained their structural integrity, enabling the researchers to evaluate the response of the samples to different medication treatments.

The treatment options tested on lymphomatous included BCL-2 inhibitors, PI3K inhibitors, and Bruton’s tyrosine kinase (BTK) inhibitors to assess their efficiency in inhibiting lymphoma cell proliferation. The model showed varying sensitivities to drugs that closely paralleled the clinical responses of the patients whose samples were used, thus reaffirming its good predictive power.

For instance, in the ex vivo setting, lymphomas taken from patients who responded favorably to BTK inhibitors had comparable sensitivity to the medication. On the other hand, lenalidomide-resistant lymphomoids from a patient showed the same resistance in the model.

These findings suggest that lymphoid could potentially show the clinician the likely responses of an individual patient to different therapeutic approaches, facilitating a great deal of progress in individualizing treatment in oncology.

Clinicians can test treatments on lymphoids grown from tumor specimens obtained from patients and identify the optimal therapy before starting actual treatment, thus allowing patients to avoid unnecessary side effects and improve their response rates.

Furthermore, in addition to their therapeutic use, the lymphomas will serve as major tools to further the knowledge of cancer. With the help of lymphomas, it is possible to elucidate complex interactions between immune cells and tumor cells during treatment and test novel treatments. Lymphomas and other cancers remain evasive for cancer researchers, presenting lymphomaids as a light beam to lead the next generation of precision treatment.

This discovery elucidates the way to breakthrough customized care in combating lymphoma, representing a key leap in the quest for personalized treatment for each cancer patient.

Journal Reference:

1. Albert Santamaria-Martínez, Justine Epiney, Divyanshu Srivastava, Daniele Tavernari, Marco Varrone, Dina Milowich, Igor Letovanec, Thorsten Krueger, Rafael Duran, Giovanni Ciriello, Anne Cairoli, Elisa Oricchio. Development of patient-derived lymphomoids with preserved tumor architecture for lymphoma therapy screening. Nature Communications 09 December 2024. DOI: 10.1038/s41467-024-55098