Understanding the immune cell dysfunction in pediatric lymphoma
Worldwide Cancer Research
Karolinska Institutet Innovations (Sweden)
Lymphoma is the third most common type of cancer among children and accounts for 10-15% of all childhood cancers. Lymphoma in children and adults are divided into three main groups; Hodgkin lymphoma, B- and T-cell lymphoma. Lymphoma stems from faulty activation of B cells and, less frequently, T cells. Upon an infection, B cells undergo affinity maturation in germinal centers. B cells in germinal centers mutate their antibody-coding genes in a process that induce DNA damage during rapid B cell proliferation. B cell transformation into lymphoma may occur because of faulty DNA repair, defects in cell division, and impaired migration and interaction with other cells during the process of mutating and selecting the best fit B cells for antibody production. Patients with inborn errors in the immune system, primary immunodeficiency diseases, are prone to develop pediatric and adolescent lymphoma of very poor prognosis. An unmet need is to understand the molecular and cellular pathophysiology to define better treatment for patients with pediatric lymphoma, both in the primary and relapse setting, and for poor prognosis lymphoma of primary immunodeficiency patients. The goal of this project is two-fold: 1) To gain molecular insight into pediatric lymphoma by analysis of single cells from lymphoma specimens and 2) To develop and use methods where specific alteration in gene expression can be examined functionally and for defining new personalized and generalized therapeutic approaches.
2.1 Biological and endogenous factors