Interactive atlas reveals immunological changes in multiple myeloma

Multiple myeloma (MM) is an incurable blood cancer that leads to weakened immunity, bone damage and other sedate health problems. High rates of relapse after initial treatment make the search for fresh immunotherapies urgent. However, the effectiveness of these therapies often depends on the functional immune microenvironment in MM patients. VIB and VUB scientists have now released an interactive tool based on a single-cell RNA sequencing (scRNA-seq) atlas of the immune microenvironment of multiple myeloma at different stages of the disease to support developers of fresh immunotherapies.

Dr. Damya Laoui (VIB-VUB Inflammation Research Center): “We have developed a comprehensive and detailed immunological atlas showing the evolution of multiple myeloma disease progression in humans and mice. This fresh tool is publicly available and has the potential to significantly contribute to the treatment of immune system diseases, stratify patients and facilitate the development of fresh and robust immunotherapeutic strategies for the treatment of multiple myeloma.”

Understanding the tumor microenvironment of multiple myeloma

Multiple myeloma (MM), characterized by the proliferation of malignant plasma cells in the bone marrow, is an incurable disease. Despite high initial response rates to various therapies, most patients eventually relapse and become multiresistant. Therefore, the search for fresh immunotherapies is ongoing. The effectiveness of immune-based therapies often depends on the functional immune microenvironment. Tools that enable in-depth analysis of the MM tumor immune microenvironment (TME) may support overcome this obstacle to therapy development.

Emma Verheye, together with her colleagues from the research teams of Damyi Laoui (VIB-VUB) and Kim De Veirman (VUB), met this need. She investigated the active changes in MM-TME of an immunocompetent MM mouse model and uncovered potential resistance mechanisms that could potentially hinder effective and robust therapeutic strategies in MM. On this basis, a comprehensive single-cell RNA sequencing atlas of the MM immune microenvironment at various stages of the disease was developed.

By correlating the immunological changes observed in our mouse dataset with those in humans at different stages of the disease, we were able to verify active changes as the disease progresses, demonstrating how closely this mouse model reflects the human condition.

Emma Verheye (VIB-VUB), first author

Recent insights into disease progression and target immune populations

The results showed that MM-TME was characterized by an boost in T lymphocytes, characterized by an exhausted phenotype. In the early stages of the disease, neutrophils appeared harmless, but as the disease progressed, they acquired pro-tumor properties. Moreover, conventional dendritic cells (cDC) were less energetic in MM, highlighting the potential of immune-boosting therapies.

Dr. Kim De Veirman (VUB): “Our novel tool has revealed that cDCs are a population that can be targeted for MM treatment. We therefore performed the first preclinical evaluation of DC-activating αCD40 therapy in murine and human samples and in MM mouse model. αCD40 administration led to effective CDC activation and subsequent T cell activation and a significant short-term antitumor response. These positive results demonstrate that we have developed a valuable research tool for the MM research community.”

Free research tool

An interactive tool based on the scRNA-seq atlas of the immune microenvironment of multiple myeloma at different stages of the disease is freely available to research teams via: www.single-cell.be/Laouimmunology/5T33MMimmunekinetics