Tumor Extracellular Vesicles: From In Vivo Biology to B Cell-Targeting Immunotherapy

My research trajectory has focused on elucidating the role of tumor-derived Extracellular
Vesicles (EVs) as key mediators of systemic immune responses. A core principle of my work is
the study of native tumor EVs in physiologically relevant in vivo settings, facilitated by
genetically engineering EV parental cells. This rigorous approach led to the discovery of a novel
EV trafficking pathway in the lymph node, where tumor EVs are captured by subcapsular sinus
(SCS) macrophages, a finding published in Science (2016).
Building on this framework, our subsequent data uncovered a novel EV → B cell axis. This work
demonstrated that despite the potential for chronic immunosuppression, the antigens contained
within these EVs are essential for generating potent, anti-tumor B cell responses. The emerging
clinical significance of B cells as key prognostic and predictive indicators in cancer highlights B
cell-mediated responses as a powerful, untapped pathway. Our data demonstrate that
EV-mediated B cell activation suppresses tumor growth even in checkpoint-resistant models
(under revision).
Leveraging the same tools for studying native EVs, we also investigated the biology of
Senescent Cell-Derived EVs (senEVs). This research demonstrated the unique
immune-modulating capabilities of senEVs, distinct from other senescence-associated factors.
By promoting senescent cell clearance, senEVs represent a novel therapeutic target to address
cancer recurrence, thus showcasing the broad applicability of our in vivo EV methodology
(Cancer Res 2025).
Based on the evidence that B cell activation via EV-bound antigens is necessary to amplify
anti-tumor responses, I now propose to translate this mechanistic insight into a tangible
therapeutic reality. My strategy is to effectively convert the native antigenic payload of
endogenous EVs into an in vivo cancer vaccine, offering a novel pathway to overcome primary
resistance and drive durable, polyclonal T cell responses in solid tumors