Follicular Lymphoma (FL) is a slow-growing type of cancer that develops when B-cells (also known as B-lymphocytes) become abnormal. B-cells are white blood cells that fight infection. The abnormal B-cells (lymphoma cells) usually accumulate in lymph nodes, but they can affect other parts of the body.
Its origin is not fully known, but they likely come from the interplay between (i) genetic alterations in the abnormal B-cells and (ii) their microenvironment. The supporting tissue formed by different cell types (non-tumor cells) and extracellular matrix provides the abnormal B-cells with an additional survival advantage. This tumor “social network” is called the tumor microenvironment (TME).
The most common diagnostic test for FL is to remove part or all of an enlarged lymph node (a biopsy). This may be done under local or general anesthetic. The biopsy is then sent to a Pathology Laboratory to be checked for lymphoma cells by a Pathologist together with additional cellular and molecular analysis.
Initial work-up should include imaging studies (computed tomography (CT) or PET-CT) and a bone marrow aspirate and biopsy. The staging is established following the Ann Arbor classification system according to the dissemination status and patient symptoms. Grading is assessed by a pathologist and is related to the proliferative index of FL.
FL is in general a low-grade lymphoma and usually develops slowly. Some patients may not need treatment for months or years. However, FL is a highly heterogeneous disease and some patients can clinically progress or undergo histological transformation (HT) to an aggressive lymphoma.
FL is still considered incurable, as this type of lymphoma usually responds to initial therapy, but the majority of patients eventually relapse. To this divergent evolution, the lymphoma “social network” or microenvironment may contribute in different flavours, especially in facilitating the escape of the abnormal B-cells from the surveillance of the patient ́s immune system in a different degree in each case. This escaping mechanism may contribute to clinical progression and HT.
TAIFOL aims to characterize the interactions between the abnormal B-cells and their immune TME. The heterogeneity of this immune TME will be grouped into four distinct scenarios based on the different clinical responses to standard chemo-immuno therapeutic regimens. We will use a mutiparametric approach using genomic, transcriptomic and imaging techniques. These results will provide the basis to design tailored immunotherapies directed to reactivate the immune system in each clinical subgroup that will be validated in state-of-the-art 3D cultures of FL patient’s cells.
