Multiple myeloma (MM) is characterized by a broad range of immune evasion strategies, that result in abnormalities in immune cell (and particularly T-cell) responses. Cumulative exposure to several anti-MM drugs reduce T-cell numbers or induce functional T-cell defects. In addition, increasing evidence suggests that the MM microenvironment, which consists of several components, including BM stromal cells (BMSCs), immune suppressor cells and immunosuppressive molecules, promotes tumor growth, impairs immune responses and limits the efficacy of anticancer treatments including T-cell redirecting bispecific antibodies.
So far, in depth understanding of the local and systemic immune dynamics during treatment with conventional flow cytometry has been restricted by the limited number of markers that can be detected simultaneously, imposing the need for large amount of input material. Most importantly, however, current immune profiling methods do not address the actual immune cell functional status.
Recently, it became clear that virtually all aspects of immune cell function, including differentiation, migration and secretion of immunomodulatory molecules, are regulated by dynamic changes in cellular metabolism. As an example, glycolysis has a crucial role in T cell effector function as well as in the immuno-stimulatory activity of antigen presenting cells, while fatty acid oxidation controls the development of regulatory T cells and tolerogenic dendritic cells. Importantly, recent groundbreaking studies revealed that the metabolic status can functionally discriminate T cell subsets sharing common phenotypic features that cannot be resolved using traditional markers. This underscores the potential of immune-metabolic profiling to uncover the immune dynamics that preclude effective antitumor immunity, and provide new insights into strategies to improve therapy response
Using cutting-edge spectral flow cytometry and cellular and molecular biology techniques, the immune-metabolic profiling team you will be part of will:
- Determine how tumor cells influence the blood and bone marrow immune landscape and functional status in multiple myeloma;
- Explore the alterations of the blood and bone marrow immune environment induced by anti-MM therapies (with a focus on T-cell redirecting bispecific antibodies)
- Explore which factors predict durable response or MRD-negativity;
- Study the mechanisms underlying immune alterations with a particular focus on communication mediated by extracellular vesicles (EVs) using relevant in vitro 3D systems.