Fotis Asimakopoulos
Job Description
Our lab has major areas of interest in 1) multiple myeloma modeling, 2) tumor microenvironment and tumor immunology and 3) novel approaches for cancer vaccines.
1) Myeloma: Our lab focuses on multiple myeloma, the second most common blood cancer. Myeloma is a growing problem in the ageing population and despite great advances in therapy in the last 15-20 years, it remains incurable for the vast majority of patients. Despite effective modern and more traditional treatment approaches, almost all patients will see their disease come back at some point in their course. For many of our patients myeloma can become a “chronic condition”: unfortunately however, the myeloma cancer cells tend to evolve more aggressive and drug-resistant with time, and when they come back, they often come back with vengeance. We are working towards the goal of making myeloma a problem that most patients can overcome and conquer for good, through the construction and application of better myeloma animal models.
2) Tumor microenvironment and tumor matrix-immune cross-talk: We are interested in the regulation of homeostasis, activation and function of intratumoral dendritic cells and macrophages. The myeloid tumor infiltrate holds the secret for improved immunotherapy efficacy whether mediated through endogenous effectors (cytotoxic T cells, NK cells) or engineered effectors (CAR-T, CAR-NK). In the last few years, we have focused on mechanisms by which tumor matrix remodeling controls the polarization and function of intratumoral myeloid antigen-presenting cells.
3) New approaches for “in situ” cancer vaccines: Turning living tumors into their own vaccines (so-called “in situ” vaccines) has emerged as a hot topic for cancer treatment in recent years. The idea is that you pour immune “gasoline” into a tumor site to ignite a hotbed of battle between immune cells and tumor cells. The result is that the body’s fighter troops (T cells, a type of immune cell) can be intensity-trained to tackle all the machinations of their crafty opponent (the cancer) and can carry on their tumor-killing mission in faraway tumor sites that they later travel to, anywhere in the body. So how do we turn living tumors into their own vaccine? By enhancing the boot-camp training of the fighter troops (T cells). How do we achieve this? By empowering the drill-sergeant cells. The drill sergeant is a type of immune cell called dendritic cell. The drill sergeant knows danger when she sees it and can train the cadets (naïve T cells) to become seasoned fighters (effector T cells). How do we empower the drill sergeant? Our lab recently defined an unexpected role for the tumor stroma (the sheath of the tumor) in controlling the behavior of the drill sergeant dendritic cells (Papadas, Cell Reports, 2022). This actually makes sense because the drill sergeants typically remain at the edge of the tumor even when the battle inside the tumor rages between the fighter troops and cancer cells. Small bits from the tumor sheath can affect the mighty drill sergeants. One of these bits, called versikine, acts like slow-release steroids for the drill sergeants. We are building on our recent discovery of versikine as a booster for drill-sergeant dendritic cells in order to generate better in situ (“living”) cancer vaccines.
