
Cellular Immunology
Cellular immunology

The immune system fights what might be dangerous to our body (e.g., virus, bacteria, exogenous substances), and innate and adaptive immunity usually tightly cooperate at this task with excellent results.
Is a growing tumor seen as dangerous by the immune system? Tumor cells possess antigens that potentially trigger an immune response. Why then, are we so frequently overwhelmed by cancer? Do cancer cells hide in tissues unnoticed to the immune system and/or find insider allies to smoothly spread? Are there environmental factors that support tumor growth by modulating the immune response?
Goal of our research is to achieve a deeper understanding of tumor cell-extrinsic mechanisms influencing interactions between transformed cells and the immune system that favor tumor progression. This knowledge is implemented to identify means whereby induce a therapeutic anti-tumor immune response.
Research activity
Our laboratory is currently pursuing the following two lines of research:
- Crosstalk between tumor cells and the surrounding stroma in the early phases of cancer spreading. Tumor cells are embedded in a stroma mostly made of fibroblasts, collagen fibers, various proteins, vessels, and immune cells. We reported that cancer cells release immunosuppressive factors (doi: 10.1158/0008-5472.CAN-14-2346), modulate local pH (doi: 10.1158/0008-5472.CAN-11-1272) and induce vessel anergy (doi: 10.4049/jimmunol.1101877. Epub 2012 Feb 8), thus generating a harsh environment for immune cells. We also devised strategies to overcome such hurdles with potential clinical applications (doi: 10.4049/jimmunol.1101877. Epub 2012 Feb 8). We are currently investigating the composition of the extracellular matrix that might favor cancer cell invasion and migration. We are also aimed at identifying immune biomarkers of response to immunotherapy in human urogenital neoplasms.
- Gut microbiota modulation to prevent progression of smoldering multiple myeloma to active disease. Multiple myeloma (MM) is a treatable but incurable neoplasm of plasma cells. Although asymptomatic smoldering MM (SMM) often precedes MM, most patients affected by SMM are only offered active observation, which increases their frustration and anxiety. In mouse models of MM, we demonstrated a direct link between the gut microbiota and T helper 17 (Th17) lymphocytes, which migrate from the gut to the bone marrow (BM) at the phase of asymptomatic disease, and favor the expansion of neoplastic plasma cells thus fueling progression to symptomatic MM. Similarly, in SMM patients, higher levels of BM IL-17 predicted accelerated disease (doi: 10.1038/s41467-018-07305-8). We aim at demonstrating in mice and humans that modulation of the gut microbiota using prebiotics, probiotics and/or postbiotics block MM progression (doi: 10.1038/s41375-023-01874-4. Epub 2023 Mar 30). We are also investigating the potential synergy between gut microbiota modulation and cancer immunotherapies.