B cell responses to tumor-derived extracellular vesicles

Extracellular vesicles (EVs) carry antigens in a particulate form. We have demonstrated for the first time that native tumor EVs drain into sentinel lymph nodes. It is widely known that lymph nodes handle particulate antigens differently from small, soluble ones: particulate antigens like viruses, bacteria and immune complexes are captured by sub-capsular sinus macrophages and relayed to B cells. In this project, we study how B cells respond to tumor antigens carried by EVs.

Four-Color CMR
Four-color confocal microscopy reconstruction (420μm depth) of a lymph node draining a squamous cell carcinoma tumor that expresses both tEV-bound (“Particulate Ag”, left) and secreted (“Soluble Ag”, right) antigens, shown separately as 3-color micrographs. Soluble antigens fill lymph node sinuses (red) whereas particulate antigens are captured by sub-capsular sinus macrophages (SSM, blue) and accumulate in structures resembling B cell follicles.

Immune response to senescence-associated extracellular vesicle

Senescent cells accumulate with age and are linked to tissue disfunction and disease. Senescent cells have profound non-autonomous effects upon immune cells, which can ultimately tip the balance toward chronic inflammatory conditions. Extracellular vesicles (EVs) play a significant role in non-autonomous signaling. In this project, we employ genetic tools to functionally study native senescence cell-derived EVs and how they promote removal of senescent cells and restoration of tissue homeostasis.

In vivo (top) and in vitro (bottom) cellular senescence induction. Gene transfer to the oral cavity and to the salivary glands by topical lentiviral vector administration (at the indicated dose). Senescence induction in head and neck squamous cancer cell lines MOC1 and MOC2 by treatment of cells with combination of chemotherapeutic agents (Cisplatin and Paclitaxel). Intensity of white indicates levels of senescence-associated B-Gal, as measured by flow cytometry.