Understanding tumor microenvironment interactions in lymphoid cancers: Translation into improved treatment outcome prediction and development of personalized therapies
Malignant lymphomas are the fifth most frequent cancer in humans, affecting patients of all ages. Despite generally effective treatments, a significant number of patients still die from the progressive disease. Interactions of the malignant cells with cells of the tumor microenvironment are increasingly recognized to play a pivotal role in the development of many lymphoma subtypes. However, the clinical potential of an improved understanding of microenvironment-related biology remains largely untapped.
Dr. Christian Steidl’s research focuses on B-cell lymphomas; in particular on the two related subtypes — Hodgkin lymphoma and primary mediastinal B-cell lymphoma — that often affect adolescents and young adults. This study will investigate tumor microenvironment interactions as therapeutic targets in B-cell lymphomas. Steidl’s team will seek to elucidate the underlying pathobiology of the tumor microenvironment, and macrophage interactions in particular, to identify novel drug targets and pave the way for the design of innovative clinical trials.
The study will also identify outcome predictors and resistance mechanisms of childhood and adult Hodgkin lymphoma. Molecular treatment outcome predictors will be developed using genomics approaches. Better outcome prediction using biological markers will identify patients at high risk and allow for personalized treatment approaches for children and adults suffering from relapsed Hodgkin lymphoma. Specifically, the recent emergence of novel targeted therapies holds the promise to overcome this high risk using these therapies to augment or replace existing therapies.
Finally, this research will define the mutational landscape of Hodgkin lymphoma and primary mediastinal B-cell lymphoma. This will involve the complete characterization of mutations by next-generation sequencing approaches. Preliminary data indicate that somatic mutations in both diseases are critically deregulating molecular pathways that might be targetable by novel therapeutic approaches. These studies will aim to transform novel findings into meaningful advances in clinical hematology.